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- Title
- Cells and cocktails: antioxidants rescue carcinogen induced mitotic defects in both chromosomally stable and unstable cells.
- Creator
- Griffin, Isabel Sloan., Harriet L. Wilkes Honors College
- Abstract/Description
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Tumor cells are characterized by an increase in genomic instability, brought about by both chromosomal rearrangement and chromosomal instability. Both of these broad changes can be induced by exposure to carcinogens. During mitosis, cells can exhibit early and late lagging chromosomes, multipolar spindles or anaphase bridges, all of which contribute to genomic rearrantement. We have studied the link between exposure to carcinogen and prevalence of mitotic defect in both chromosomally stable...
Show moreTumor cells are characterized by an increase in genomic instability, brought about by both chromosomal rearrangement and chromosomal instability. Both of these broad changes can be induced by exposure to carcinogens. During mitosis, cells can exhibit early and late lagging chromosomes, multipolar spindles or anaphase bridges, all of which contribute to genomic rearrantement. We have studied the link between exposure to carcinogen and prevalence of mitotic defect in both chromosomally stable and unstable cell lines as well as ecamined the restorative effects of antioxidants in preventing mitotic defects. We have exposed MES-SA uterine cancer cells to vinyl chloride followed by exposure to an antioxidant : ascorbic acid, B-carotene, or lycopene. Treated cells were then scored for the prevalence of mitotic defects within the population and compared to controls. We have also investigated whether pre-treatment with the antioxidants will weaken the effects of carcinogen exposure in these cell lines.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3359304
- Subject Headings
- Cellular signal transduction, Cell differentiation, Medical genetics, Cancer, Genetic aspects, Antioxidants, Therapeutic use, Cancer, Chemoprevention, Apoptosis, Molecular aspects, Genetic regulation
- Format
- Document (PDF)
- Title
- Cellular Basis of Sponge-Sponge Associations.
- Creator
- Conkling, Megan, Pomponi, Shirley A., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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Marine sponges interact and coexist with many different organisms. A two-sponge association between Amphimedon erina and Geodia gibberosa commonly occurs in the Florida Keys. Previous studies have only focused on the ecological influence of the association; they did not examine the cellular basis of the association. This association between A. erina and G. gibberosa was used in the development of an in vitro model to further the understanding of the cellular basis of natural sponge-sponge...
Show moreMarine sponges interact and coexist with many different organisms. A two-sponge association between Amphimedon erina and Geodia gibberosa commonly occurs in the Florida Keys. Previous studies have only focused on the ecological influence of the association; they did not examine the cellular basis of the association. This association between A. erina and G. gibberosa was used in the development of an in vitro model to further the understanding of the cellular basis of natural sponge-sponge associations. In this study, sponge cells were cultured individually and in co-cultures and their responses related to apoptosis, cell death, and proliferation were monitored using high content imaging. Co-cultured cells of species that form sponge-sponge associations did not have the same cellular responses compared to co-cultured cells of species that do not form sponge-sponge associations. Protein expression analyses demonstrated that the model that was established does not mimic the cellular response of the association in nature, but this model can be used to test in vitro cellular interactions of sponge species that do not form associations in nature. In addition, the protein expression data that were obtained revealed that sponges use similar apoptotic pathways as humans and suggest that sponge cells may shut down cell cycling in order to repair damaged DNA. This research is a small piece to the puzzle that is sponge cell culture research.
Show less - Date Issued
- 2017
- PURL
- http://purl.flvc.org/fau/fd/FA00004848, http://purl.flvc.org/fau/fd/FA00004848
- Subject Headings
- Sponges--Habitat--Florida., Marine invertebrates--Florida., Aquatic invertebrates--Cultures and culture media., Apoptosis., Cell culture., Symbiosis.
- Format
- Document (PDF)
- Title
- The Impact of Pharmacological Targeting of Abnormal Tumor Metabolism with 3-Bromopyruvate on Dendritic Cell Mediated Tumoral Immunity.
- Creator
- Lang, Kevin, Hartmann, James X., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Studies have shown that tumor cells are susceptible to pharmacological targeting of their altered glycolytic metabolism with a variety of compounds that result in apoptosis. One such compound, 3-bromopyruvate (3-BP), has been shown to eradicate cancer in an animal model. However, no studies have shown whether the apoptotic fragments resulting from 3-BP treatment have the capacity to elicit an immunogenic cell death that activates dendritic cells, the primary antigen presenting cell in the...
Show moreStudies have shown that tumor cells are susceptible to pharmacological targeting of their altered glycolytic metabolism with a variety of compounds that result in apoptosis. One such compound, 3-bromopyruvate (3-BP), has been shown to eradicate cancer in an animal model. However, no studies have shown whether the apoptotic fragments resulting from 3-BP treatment have the capacity to elicit an immunogenic cell death that activates dendritic cells, the primary antigen presenting cell in the immune system. Immunogenic cell death is critical to eliciting an effective adaptive immune response that selectively kills additional target cells and generates immunological memory. We demonstrated that 3-bromopyruvate induced apoptosis in a number of different murine breast cancer cell lines, including the highly metastatic 4T1 line. The dying tumor cells stimulated immature dendritic cells (DCs) of the immortal JAWS II cell line to produce high levels of the pro-inflammatory cytokine IL-12, and increased their expression of key co-stimulatory molecules CD80 and CD86. The activated dendritic cells showed increased uptake of fragments from dying tumor cells that correlated with the increased levels of calreticulin on the surface and release of high group motility box 1 (HMGB1) of the latter following 3-BP treatment. Additionally, the anti-phagocytic signal CD47 present on breast cancer cells was reduced by treatment with 3-bromopyruvate when compared to the levels on untreated 4T1 cells. 3-BP treated breast cancer cells were able to activate dendritic cells through TLR4 signaling. Signaling was dependent on both the expression of surface calreticulin and on the extracellular release of high mobility group box 1 protein (HMGB1) during the process of immunogenic cell death. Killing by 3-BP was compared to mitoxantrone and doxorubicin, among the few chemotherapeutics that induce immunogenic cell death. 3-BP killing was likewise compared to camptothecin, a compound that fails to induce immunogenic cell death. Importantly, 3-BP did not markedly decrease the levels of the key peptide presenting molecule MHC I on DCs that were co-cultivated with dying tumor cells. Treatment of the highly aggressive triple negative BT-20 human breast cancer cell line with 3-BP also induced an immunogenic cell death, activating human dendritic cells in vitro.
Show less - Date Issued
- 2017
- PURL
- http://purl.flvc.org/fau/fd/FA00004834
- Subject Headings
- Apoptosis., Cellular signal transduction., Cell death., Breast--Cancer--Treatment., Carrier proteins., Cancer--Molecular aspects., Biological interfaces.
- Format
- Document (PDF)
- Title
- Anticancer activity of two dietary phytochemicals: Genistein and beta-lapachone.
- Creator
- Merchant, Kendra T., Florida Atlantic University, Kumi-Diaka, James
- Abstract/Description
-
Phytochemicals are biologically active secondary plant metabolites that have been shown to exhibit anti-cancer activity. The dietary phytochemicals genistein isoflavone and beta-lapachone, were investigated to determine their effect on the growth of human prostate adenocarcinoma cells in vitro. The cells were exposed to varying concentrations of both phytochemicals in single and combination treatments for specified time periods and their effect was determined using post-treatment cell...
Show morePhytochemicals are biologically active secondary plant metabolites that have been shown to exhibit anti-cancer activity. The dietary phytochemicals genistein isoflavone and beta-lapachone, were investigated to determine their effect on the growth of human prostate adenocarcinoma cells in vitro. The cells were exposed to varying concentrations of both phytochemicals in single and combination treatments for specified time periods and their effect was determined using post-treatment cell viability, treatment-induced apoptosis and cell signaling assays. The overall results revealed that both phytochemicals inhibited cell growth and proliferation and induced apoptosis in a dose-dependent manner for both single and combination treatments. However, combination treatments were not significantly more effective than single treatment with either drug. Both phytochemicals could therefore offer therapeutic efficacy in human prostate adenocarcinoma.
Show less - Date Issued
- 2005
- PURL
- http://purl.flvc.org/fcla/dt/13250
- Subject Headings
- Phytochemicals--Physiological effect, Prostate--Cancer--Molecular aspects, Apoptosis--Molecular aspects, Prostate--Cancer--Treatment
- Format
- Document (PDF)
- Title
- Polyglutamine aggregates stimulate ER stress and trigger apoptosis by activating BH-3 only protein Bim.
- Creator
- Bhagavatula, Nithya, Wei, Jianning, Florida Atlantic University
- Abstract/Description
-
Huntington's disease (HD) is an inherited neurological disorder characterized by a selective loss of neurons in the striatum and cortex leading to involuntary movement, dementia and eventually cell death. HD is caused by an expanded polyglutamine (PolyQ) repeat in Huntingtin (Htt) protein. It is well known that misfolded mutant Htt could form intracellular aggregates, trigger ER stress and ultimately lead to apoptosis. However, the molecular link between ER stress and apoptosis in...
Show moreHuntington's disease (HD) is an inherited neurological disorder characterized by a selective loss of neurons in the striatum and cortex leading to involuntary movement, dementia and eventually cell death. HD is caused by an expanded polyglutamine (PolyQ) repeat in Huntingtin (Htt) protein. It is well known that misfolded mutant Htt could form intracellular aggregates, trigger ER stress and ultimately lead to apoptosis. However, the molecular link between ER stress and apoptosis in mitochondria is poorly understood. In the present study, we identified Bim (Bcl-2 interacting mediator of cell death) as the essential protein. We first established a cellular model of HD by over expressing the Nterminus of wild type and mutant Htt into HEK293 cell lines. We showed that the accumulation and aggregation of misfolded mutant Htt protein triggers ER stress and apoptosis. The Bim protein expression level was greatly increased in mutant Htt transfected cells and this increase was partially due to up-regulation of Bim mRNA as analyzed using quantitative RT-PCR. We further showed that Bim phosphorylation also played an important role in regulating Bim expression. Moreover, up-regulation of Bim facilitates the translocation of Bax to mitochondrial membrane, which lead to cytochrome c release and apoptosis. We also silenced Bim using siRNA to further investigate the essential role of Bim in mutant Htt induced ER stress and apoptosis. Identifying the Bim pathway that is altered in response to the mutant Htt protein is important for understanding the cellular processes impacted by the disease.
Show less - Date Issued
- 2008
- PURL
- http://purl.flvc.org/fau/fd/FA00000726
- Subject Headings
- Nervous system--Degeneration--Molecular aspects, Apoptosis, Cellular signal transduction, Huntington's disease--Genetic aspects, Huntington's disease--Pathophysiology
- Format
- Document (PDF)
- Title
- Therapeutic Options for the Treatment of Breast Cancer: Using Cytoreg and Genistein Isoflavone.
- Creator
- Johnson, Michelle M., Kumi-Diaka, James, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
In spite the heavy investments in therapeutic research breast cancer still impacts the lives of women globally. The projected incidence of new cases in USA for 2008 is 67,770, with estimated 40,480 deaths. In this study, we investigated the therapeutic efficacy of Cytoreg®-genistein combination treatment on MCF-7 human breast cancer cells. MCF-7 cells were treated with genistein and Cytoreg® single and combination treatments for 24- 48hr; and the chemosensitivity assessed using bioassays:...
Show moreIn spite the heavy investments in therapeutic research breast cancer still impacts the lives of women globally. The projected incidence of new cases in USA for 2008 is 67,770, with estimated 40,480 deaths. In this study, we investigated the therapeutic efficacy of Cytoreg®-genistein combination treatment on MCF-7 human breast cancer cells. MCF-7 cells were treated with genistein and Cytoreg® single and combination treatments for 24- 48hr; and the chemosensitivity assessed using bioassays: Trypan Blue and MTT for cell viability; Ethidium bromide/Rhodamine 123 to assess apoptosis induction; F AM PolyCaspase binding assay for mechanism of action. The overall data indicated dose- and timedependent cell death in the MCF-cells and that apoptosis was the major means of treatmentinduced growth inhibition. There was evidence of Cytoreg®-induced autophagy in the cells. The overall findings indicated that genistein-Cytoreg® combination was more efficacious than either genistein or Cytoreg® alone. Cytoreg® enhanced the phytosensitivity of MCF-7 cells to genistein isoflavone.
Show less - Date Issued
- 2008
- PURL
- http://purl.flvc.org/fau/fd/FA00000777
- Subject Headings
- Breast--Cancer--Treatment, Phytochemicals--Physiological effect, Apoptosis--Molecular aspects, Phytoestrogens--Health aspects, Outcome assessment (Medical care)
- Format
- Document (PDF)
- Title
- Initial evaluation of organotin monomers and polymers as potential anticancer agents.
- Creator
- Doucette, Randy D., Florida Atlantic University, Louda, Deborah W.
- Abstract/Description
-
A large number of metal-containing compounds show significant activity against cancer cells and incorporating a metal into a polymer offers several possible advantages. Compounds of the type R2SnCl2 (R = methyl, ethyl, propyl, butyl, t-butyl, octyl and phenyl) were tested for the ability to inhibit the growth of Balb 3T3 mouse fibroblast cells and CAOV3 human ovarian carcinoma cells. Polymers of 2-chloro-1,4-benzenediamine and the same organotin dichloride were synthesized and tested as well....
Show moreA large number of metal-containing compounds show significant activity against cancer cells and incorporating a metal into a polymer offers several possible advantages. Compounds of the type R2SnCl2 (R = methyl, ethyl, propyl, butyl, t-butyl, octyl and phenyl) were tested for the ability to inhibit the growth of Balb 3T3 mouse fibroblast cells and CAOV3 human ovarian carcinoma cells. Polymers of 2-chloro-1,4-benzenediamine and the same organotin dichloride were synthesized and tested as well. For both monomers and polymers, the pattern of growth inhibition relative to the R group was butyl > propyl = t-butyl = octyl = phenyl > ethyl > methyl. This and other aspects of the structure-activity relationship of the monomers and polymers were examined.
Show less - Date Issued
- 2006
- PURL
- http://purl.flvc.org/fcla/dt/13410
- Subject Headings
- Apoptosis--Molecular aspects, Polymeric composites, Organometallic compounds, Cancer--Molecular aspects, Antineoplastic agents--Testing, Polymers in medicine
- Format
- Document (PDF)
- Title
- Mechanism of neuroprotection in stroke-related models.
- Creator
- Pan, Chunliu., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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Stroke is the third leading cause of mortality in the United States, and so far, no clinical interventions have been proved truly effective in stroke treatment. Stroke my result in hypoxia, glutamate release and oxidative stress, etc. The purpose of this dissertation study is to evaluate the neuroprotective effects of four drugs (taurine, G-CSF sulindac and DETC-MeSO) on PC12 cell line or primary cortical neuronal cell culture, and to understand the protective mechanisms underlying in three...
Show moreStroke is the third leading cause of mortality in the United States, and so far, no clinical interventions have been proved truly effective in stroke treatment. Stroke my result in hypoxia, glutamate release and oxidative stress, etc. The purpose of this dissertation study is to evaluate the neuroprotective effects of four drugs (taurine, G-CSF sulindac and DETC-MeSO) on PC12 cell line or primary cortical neuronal cell culture, and to understand the protective mechanisms underlying in three stroke-related models : hypoxia, excessive glutamtate and oxidative stress. In the first part of this dissertation, we studied the neuroprotection of taurine against oxidative stress induced by H2O2 in PC12 cells. Our results show that extracellular taurine exerts a neuroprotective function by restoring the expression of Bcl-2 and downregulation of the three Endoplasmic Reticulum (ER) stress markers : GRP78, Bim and CHOP/GADD153, suggesting that ER stress can be provoked by oxidative stress and can be suppressed by taurine. In the second part, glutamate excitotoxicity-induced ER stress was studied with dose and time as variables in primary cortical neurons. The results demonstrate that glutamate excitotoxicity leads to the activation of three ER stress pathways (PERK, ATF6 and IRE1) by initiating PERK first, ATF6 second and IRE1 pathway last. The third part of this dissertation studied the robust and beneficial protection of taurine in cortical neurons under hypoxia/reoxygenation or glutamate toxicity condition. We found that taurine suppresses the up-regulation of GRP778, Bim, caspase-12 and GADD153/CHOP induced by excessive glutamate or hypoxia/reoxygenation, suggesting that taurine may exert a protective function against hypoxia/regeneration by reducing the ER stress., Moreover, taurine can down-regulate the ratio of cleaved ATF6 and full length ATF6, and p-IRE1 expresssion, indicating that taurine inhibits the ER stress induced by hypoxia/reoxygenation or glutamate through suppressing ATF6 and IRE1 pathways. In the fourth part, the synergistic benefits of the combination of taurine and G-CSF, and the neuroprotective effects of G-CSF, sulindac or DETC-MeSO are studied in cortical neurons. Our results show that G-CSF, sulindac or DETC-MeSO can highly increase the neuron visibility by inhibiting ER stress induced by hypoxia/reoxygenation or glutamate toxicity. Furthermore, we proved that G-CSF or sulindac can significantly inhibit the activation of ATF6 or IRE1 pathway stimulated by hypoxia/reoxygenation, and DETC-MeSO can suppress the activation of both PERK and IRE1 pathways in primary neuron cultures. These findings provide promising and rational strategies for stroke therapy.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3352284
- Subject Headings
- Sulindac, Physiological effect, Taurine, Physiological effect, Cerebral ischemia, Prevention, Biochemical markers, Diagnostic use, Apoptosis, Oxidation reduction reaction
- Format
- Document (PDF)
- Title
- Novel molecular targets for genistein in prostate cancer cells.
- Creator
- Merchant, Kendra T., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Prostate cancer is the most common form of non-skin cancer and the second leading cause of cancer deaths within the United States. The five year survival rate has increased from 69% to 99% over the last 25 years for the local and regional disease, but has remained fairly low (approximately 34%) for the advanced disease. Therefore, current research is aimed at finding complementary or alternative treatments that will specifically target components of the signal transduction, cell-cycle and...
Show moreProstate cancer is the most common form of non-skin cancer and the second leading cause of cancer deaths within the United States. The five year survival rate has increased from 69% to 99% over the last 25 years for the local and regional disease, but has remained fairly low (approximately 34%) for the advanced disease. Therefore, current research is aimed at finding complementary or alternative treatments that will specifically target components of the signal transduction, cell-cycle and apoptosis pathways to induce cell death, with little or no toxic side effects to the patient. In this study we investigated the effect of genistein on expression levels of genes involved in these pathways. Genistein is a (4 , 5 , 7-trihydroxyisoflavone) is a major isoflavone constituent of soy that has been shown to inhibit growth proliferation and induce apoptosis in cancer cells. The mechanism of genistein-induced cell death and potential molecular targets for genistein in LNCaP prostate cancer c ells was investigated using several techniques. The chemosensitivity of genistein towards the prostate cancer cells was investigated using the ATP and MTS assays and apoptosis induction was determined using apoptosis and caspase assays. Several molecular targets were also identified using cDNA microarray and RT-PCR analysis. Our results revealed that genistein induces cell death in a time and dose-dependent manner and regulates expression levels of several genes involved in carcinogenesis and immunogenicity. Several cell cycle genes were down-regulated, including the mitotic kinesins, cyclins and cyclin dependent kinases, indicating that genistein is able to halt cell cycle progression through the regulation of genes involved in this process., Several members of the Bcl-2 family which are involved in apoptosis were also affected and a number of genes involved in immunogenicity were up-regulated including the DefB1 and HLA membrane receptors. The results of this study provide evidence of genistein's ability to inhibit growth proliferation and induce apoptosis and indicates its potential as an adjuvant in chemotherapy and immunotherapy.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/192986
- Subject Headings
- Prostate, Cancer, Adjuvant treatment, Prostate, Cancer, Molecular aspects, Apoptosis, Molecular aspects, Phytochemicals, Physiological effect, Cellular signal transduction
- Format
- Document (PDF)
- Title
- The Single Minded 2 Gene (SIM2) and Cancer: Harnessing Micro-Array Data to Facilitate Pathway Discovery and Validation.
- Creator
- Aleman, Mireille J., Narayanan, Ramaswamy, Florida Atlantic University
- Abstract/Description
-
A Down's Syndrome related Single Minded 2 gene (SIM2), previously known to be associated with Trisomy 21 was predicted by bioinformatics to be colon cancer specific. In previous work from the laboratory using a patient tissue repository, an isoform of this gene, short form (SIM2-s) was shown to be colon cancer specific. Inhibition of SIM2-s expression by antisense technology resulted in cancer-cell specific apoptosis within 24 hours. Microarray-based gene expression profiling of the antisense...
Show moreA Down's Syndrome related Single Minded 2 gene (SIM2), previously known to be associated with Trisomy 21 was predicted by bioinformatics to be colon cancer specific. In previous work from the laboratory using a patient tissue repository, an isoform of this gene, short form (SIM2-s) was shown to be colon cancer specific. Inhibition of SIM2-s expression by antisense technology resulted in cancer-cell specific apoptosis within 24 hours. Microarray-based gene expression profiling of the antisense-treated colon cancer cells provided a fingerprint of genes involving key cell cycle, apoptosis, DNA damage and differentiation genes. Taking hints from the microarray database, experiments were initiated to decipher the molecular mechanism underlying the cancer specific function of the SIM2-s gene. Using an isogenic cell system, apoptosis was found to be dependent on DNA damage and repair gene, GADD45-a. Further, key pathways including p38 MAP kinase (MAPK) and specific caspases were essential for apoptosis. Programmed cell death was not dependant on cell cycle and was preceded by the induction of terminal differentiation. To clarify whether SIM2-s function is a critical determinant of differentiation, stable transfectants of SIM2-s were established in a murine adipocytic cell line (3T3-L 1 ). SIM2-s overexpression caused a pronounced block of differentiation of the pre-adipocytes into mature adipocytes. A study of the differentiation pathway in 3T3-L 1 cells suggested that this block occurs early on in the cascade. These results supported the starting premise that SIM2-s is a critical mediator of cell differentiation. To clarify whether the SIM2-s gene has transforming potential, the SIM2-s gene was overexpressed in the NIH3T3 murine fibroblast cell line. The cells expressing the human SIM2-s gene exhibited shorter doubling time, abrogation of growth serum requirement, greater cell number at saturation density and focus formation. In vivo tumorigenicity assays showed tumor formation with long latency. These results provide strong evidence for the role of SIM2-s gene in tumor cell growth and differentiation, and validate drug therapy use for the gene.
Show less - Date Issued
- 2007
- PURL
- http://purl.flvc.org/fau/fd/FA00000845
- Subject Headings
- Cancer--Genetic aspects, DNA microarrays--Diagnostic use, Apoptosis--Molecular aspects, Medical informatics, Gene expression--Research--Methodology
- Format
- Document (PDF)
- Title
- Autophagy gene atg-18 regulates C. elegans lifespan cell nonautonomously by neuropeptide signaling.
- Creator
- Minnerly, Justin, Jia, Kailiang, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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In the round worm C. elegans, it has recently been shown that autophagy, a highly conserved lysosomal degradation pathway that is present in all eukaryotic cells, is required for maintaining healthspan and for increasing the adult lifespan of worms fed under dietary restriction conditions or with reduced IGF signaling. It is currently unknown how extracellular signals regulate autophagy activity within different tissues during these processes and whether autophagy functions cell-autonomously...
Show moreIn the round worm C. elegans, it has recently been shown that autophagy, a highly conserved lysosomal degradation pathway that is present in all eukaryotic cells, is required for maintaining healthspan and for increasing the adult lifespan of worms fed under dietary restriction conditions or with reduced IGF signaling. It is currently unknown how extracellular signals regulate autophagy activity within different tissues during these processes and whether autophagy functions cell-autonomously or nonautonomously. We have data that for the first time shows autophagy activity in the neurons and intestinal cells plays a major role in regulating adult lifespan and the longevity conferred by altered IGF signaling and dietary restriction, suggesting autophagy can control these phenotypes cell non-autonomously. We hypothesize that autophagy in the neurons and intestinal cells is an essential cellular process regulated by different signaling pathways to control wild type adult lifespan, IGF mediated longevity and dietary restriction induced longevity. Excitingly we also have found that in animals with reduced IGF signaling autophagy can control longevity in only a small subset of neurons alone. Autophagy in either specific individual chemosensory neurons or a small group of them is completely sufficient to control IGF mediated longevity. This work provides novel insight to the function and regulation of autophagy which will help shed light on understanding this essential process in higher organisms, including mammals.
Show less - Date Issued
- 2017
- PURL
- http://purl.flvc.org/fau/fd/FA00004862, http://purl.flvc.org/fau/fd/FA00004862
- Subject Headings
- Caenorhabditis elegans--Molecular genetics., Aging--Molecular aspects., Life cycles (Biology), Cell death., Gene expression., Autophagic vacuoles., Apoptosis., Eukaryotic cells.
- Format
- Document (PDF)
- Title
- Anticancer ativities of topotecan-genistein combination in prostate cancer cells.
- Creator
- Hörmann, Vanessa P., Kumi-Diaka, James, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Prostate cancer is one of the leading causes of death in men aged 40-55. Genistein isoflavone (4', 5', 7-trihydroxyisoflavone) is a dietary phytochemical with demonstrated anti-tumor activities in a variety of cancers. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy drug, primarily used for secondary treatment of ovarian,cervical and small cell lung cancers. This study was to demonstrate the potential anticancer activities and synergy of topotecan-genistein combination in...
Show moreProstate cancer is one of the leading causes of death in men aged 40-55. Genistein isoflavone (4', 5', 7-trihydroxyisoflavone) is a dietary phytochemical with demonstrated anti-tumor activities in a variety of cancers. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy drug, primarily used for secondary treatment of ovarian,cervical and small cell lung cancers. This study was to demonstrate the potential anticancer activities and synergy of topotecan-genistein combination in LNCaP prostate cancer cells. The potential efficacy and mechanism of topotecan/genistein-induced cell death was investigated... Results: The overall data indicated that i) both genistein and topotecan induce cellular death in LNCaP cells, ii) topotecan-genistein combination was significantly more efficacious in reducing LNCaP cell viabiligy compared to either genistein or topotecan alone, iii) in all cases, cell death was primarily through apoptosis, via the activation of the intrinsic pathway, iv) ROS levels were increased and VEGF expression was diminished significantly with the topotecan-genistein combination treatment, v) genetic analysis of topotecan-genistein treatment groups showed changes in genetic expression levels in pathway specific apoptotic genes.... Conclusion: Treatments involving topotecan-genistein combination may prove to be an attractive alternative phytotherapy of adjuvant therapy for prostate cancer.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3358553
- Subject Headings
- Apoptosis, Molecular aspects, Prostate, Cancer, Adjuvant treatment, Prostate, Cancer, Molecular aspects, Phytochemicals, Physiological effect, Antioxidants, Therapeutic use, Topotecan, Therapeutic use, Genistein, Therapeutic use, Cancer, Chemotherapy
- Format
- Document (PDF)
- Title
- Developmental and Protective Mechanisms of the Ocular Lens.
- Creator
- Chauss, Daniel C., Kantorow, Marc, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biomedical Science
- Abstract/Description
-
The vertebrate eye lens functions to focus light onto the retina to produce vision. The lens is composed of an anterior monolayer of cuboidal epithelial cells that overlie a core of organelle free fiber cells. The lens develops and grows throughout life by the successive layering of lens fiber cells via their differentiation from lens epithelial cells. Lens developmental defect and damage to the lens are associated with cataract formation, an opacity of the lens that is a leading cause of...
Show moreThe vertebrate eye lens functions to focus light onto the retina to produce vision. The lens is composed of an anterior monolayer of cuboidal epithelial cells that overlie a core of organelle free fiber cells. The lens develops and grows throughout life by the successive layering of lens fiber cells via their differentiation from lens epithelial cells. Lens developmental defect and damage to the lens are associated with cataract formation, an opacity of the lens that is a leading cause of visual impairment worldwide. The only treatment to date for cataract is by surgery. Elucidating those molecules and mechanisms that regulate the development and lifelong protection of the lens is critical toward the development of future therapies to prevent or treat cataract. To determine those molecules and mechanisms that may be important for these lens requirements we employed high-throughput RNA sequencing of microdissected differentiation statespecific lens cells to identify an extensive range of transcripts encoding proteins expressed by these functionally distinct cell types. Using this data, we identified differentiation state-specific molecules that regulate mitochondrial populations between lens epithelial cells that require the maintenance of a functional population of mitochondria and lens fiber cells that must eliminate their mitochondria for their maturation. In addition, we discovered a novel mechanism for how lens epithelial cells clear apoptotic cell debris that could arise from damage to the lens and found that UVlight likely compromises this system. Moreover, the data herein provide a framework to determine novel lens cell differentiation state-specific mechanisms. Future studies are required to determine the requirements of the identified molecules and mechanisms during lens development, lens defense against damage, and cataract formation.
Show less - Date Issued
- 2016
- PURL
- http://purl.flvc.org/fau/fd/FA00004577
- Subject Headings
- Eye--Diseases--Etiology., Cell differentiation., Cellular signal transduction., Protein folding., Mitochondrial pathology., Cellular control mechanisms., Apoptosis., Oxidative stress--Prevention.
- Format
- Document (PDF)
- Title
- Enhancement of the Chemopreventive and Chemotherapeutic Effects of Genistein and Beta-lapachone in Human Prostate Cancer Cells by Pyroelectrically Generated Very Low Dose Ionizing Radiation.
- Creator
- Oseni, Saheed Oluwasina, Kumi-Diaka, James, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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An estimated 220,800 new prostate cancer cases and 27,540 deaths are expected to occur in US men by the end of 2015. Despite the increased treatment modes for prostate cancer, there is still no definite cure, and prognosis remains, at best, cautiously optimistic. The explicit amalgamation of two or more cancer therapeutic modalities such as surgery, radiation, and chemotherapy, has been one of the main interests of clinical investigation for several decades. Genistein (GN) and Beta-lapachone ...
Show moreAn estimated 220,800 new prostate cancer cases and 27,540 deaths are expected to occur in US men by the end of 2015. Despite the increased treatment modes for prostate cancer, there is still no definite cure, and prognosis remains, at best, cautiously optimistic. The explicit amalgamation of two or more cancer therapeutic modalities such as surgery, radiation, and chemotherapy, has been one of the main interests of clinical investigation for several decades. Genistein (GN) and Beta-lapachone (BL) are two of the most promising anticancer phytochemical compounds. However, the anticancer activities of BL have been correlated with the enzyme activity of NQO1. The aim of this study was to investigate the enhancing effects of VLDR derived from a portable pyroelectric crystal generator on the chemopreventive and/or chemotherapeutic effects of GN and BL in NQO1+ PC3 and NQO1± (deficient) LNCaP prostate cancer cells (PCa) in vitro. The combination treat ment-induced cytotoxicity was investigated via MTT and Trypan blue exclusion assays. Dicoumarol (an NQO1 inhibitor) was co-administered to assess the effect of VLDR on NQO1 modulation. Nitro-blue tetrazolium assay was used to assess the intracellular ROS levels. Fluorescence microscopy was also used to assess the mode of cell death. In this study, a novel quantitative modeling approach was employed to comparably assess the cytotoxic effects of specific drugs used alone or in combinations with VLDR and to predict the potential synergistic therapeutic combinations. The data suggests that VLDR induced a rise in ROS levels, followed by upregulation in NQO1 levels. Pharmacodynamic indices were developed to quantify and characterize the combination treatment as synergistic, additive or antagonistic per dose or time-interval. Synergism was found to be dose and time-interval dependent. The major mode of cell death by this combination therapeutic regimen was found to be via apoptosis . In conclusion, our results confirm that VLDR enhanced cytotoxicity effects of both drugs dose- and time-dependently.
Show less - Date Issued
- 2015
- PURL
- http://purl.flvc.org/fau/fd/FA00004530, http://purl.flvc.org/fau/fd/FA00004530
- Subject Headings
- Apoptosis -- Molecular aspects, Genistein -- Therapeutic use, Phytochemicals -- Physiological effect, Phytochemicals -- Therapeutic use, Prostate -- Cancer -- Adjuvant treatment, Prostate -- Cancer -- Cryptopathology, Prostate -- Cancer -- Molecular aspects
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- Document (PDF)
- Title
- Impact of Vitamin C on Genistein-Induced Apoptosis in Prostate Cancer.
- Creator
- Famuyiwa, Toluleke, Kumi-Diaka, James, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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This study determined the impact of vitamin C dose on genistein-induced apoptosis in LNCaP cancer cells at various treatment regimens in vitro. Although the linear regression of viability assay (MTT) indicated a p-value = 0.11; NBT assay reveal a declining SOD activity during cell death. Apoptosis induction was the main mode of treatment induced cell death. The overall data showed the trend of treatment efficacy as;(Gen 10uM + Vit C 40uM) > (Gen 30uM + Vit C 40uM) > (Gen 70uM + Vit C 40uM) >...
Show moreThis study determined the impact of vitamin C dose on genistein-induced apoptosis in LNCaP cancer cells at various treatment regimens in vitro. Although the linear regression of viability assay (MTT) indicated a p-value = 0.11; NBT assay reveal a declining SOD activity during cell death. Apoptosis induction was the main mode of treatment induced cell death. The overall data showed the trend of treatment efficacy as;(Gen 10uM + Vit C 40uM) > (Gen 30uM + Vit C 40uM) > (Gen 70uM + Vit C 40uM) > 10uM genistein > 70uM genistein. The chi-square test for comparing necrosis, apoptosis and life cells showed that Vitamin C could impact genistein-induced apoptosis in LNCaP cells (p = 0.0003). This study forms the basis for in vivo studies of the impact of vitamin C on genistein-induced apoptosis in LNCaP prostate cancer cells.
Show less - Date Issued
- 2015
- PURL
- http://purl.flvc.org/fau/fd/FA00004497, http://purl.flvc.org/fau/fd/FA00004497
- Subject Headings
- Apoptosis -- Molecular aspects, Cellular signal transduction, Genistein -- Therapeutic use, Phytochemicals -- Physiological effect, Phytochemicals -- Therapeutic use, Prostate -- Cancer -- Adjuvant treatment, Prostate -- Cancer -- Molecular aspects, Vitamin C -- Therapeutic use
- Format
- Document (PDF)
- Title
- Anti-cancer activity of pomegranate (Punica granatum ) extracts in testicular cancer.
- Creator
- Brown, Jayann Marie, Florida Atlantic University, Kumi-Diaka, James
- Abstract/Description
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Recent advancement in chemotherapy has resulted in higher and longer survival rates of testicular cancer patients. However the use of chemotherapeutic agents are not without serious, sometimes fatal side effects. This study investigated the potential therapeutic efficacy of pomegranate extracts in testis cancer cells, GC1-spg, in vitro. A battery of assays was used to determine the chemosensitivity of GC1-spg cells to two pomegranate extracts, S (seed) and P (pericarp), in single and...
Show moreRecent advancement in chemotherapy has resulted in higher and longer survival rates of testicular cancer patients. However the use of chemotherapeutic agents are not without serious, sometimes fatal side effects. This study investigated the potential therapeutic efficacy of pomegranate extracts in testis cancer cells, GC1-spg, in vitro. A battery of assays was used to determine the chemosensitivity of GC1-spg cells to two pomegranate extracts, S (seed) and P (pericarp), in single and combination treatments: MTS and LDH to determine post-treatment survival rate (growth inhibition) and cytotoxicity respectively; Acridine Orange/Ethidium Bromide fluorescent dye to assess treatment-induced apoptosis/necrosis; Annexin V-FITC and TUNEL assays for early and late apoptosis respectively. Results from the obtained data indicated that both extracts have significant cytotoxic effect on testicular cancer cells (GC1-spg) in single and combination treatments. The data revealed a dose and time dependency of chemosensitivity to both extracts; and that apoptosis was the major mechanism treatment-induced cell death. Synergism was also indicated in growth inhibition by combination treatment. These findings offer strong justification for further studies with pomegranate as potential phytotherapy.
Show less - Date Issued
- 2004
- PURL
- http://purl.flvc.org/fcla/dt/13154
- Subject Headings
- Testis--Cancer--Treatment, Generative organs, Male--Diseases--Treatment, Phytochemicals--Physiological effect, Cancer--Adjuvant treatment, Apoptosis--Molecular aspects
- Format
- Document (PDF)
- Title
- Molecular pathway identification using microarray technology.
- Creator
- Tress, Matthew David., Florida Atlantic University, Narayanan, Ramaswamy
- Abstract/Description
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Harnessing the human genome using bioinformatics lead to the discovery of a highly cancer-selective gene, Single Minded 2 gene (SIM2). An isoform of the SIM2 gene, the short-form (SIM2-s), was shown to be specific to colon, pancreas, and prostate tumors. Antisense inhibition of SIM2-s in a colon carcinoma derived cell line (RKO) caused inhibition of gene expression, growth inhibition and apoptosis in vitro and in nude mice tumorigenicity models. To understand the mechanism of Sim2-s antisense...
Show moreHarnessing the human genome using bioinformatics lead to the discovery of a highly cancer-selective gene, Single Minded 2 gene (SIM2). An isoform of the SIM2 gene, the short-form (SIM2-s), was shown to be specific to colon, pancreas, and prostate tumors. Antisense inhibition of SIM2-s in a colon carcinoma derived cell line (RKO) caused inhibition of gene expression, growth inhibition and apoptosis in vitro and in nude mice tumorigenicity models. To understand the mechanism of Sim2-s antisense, the antisense treated RKO colon cancer cells were monitored for genome wide expression using Affymetrix GeneChipRTM technology. A list of apoptosis related genes was generated using GeneSpringRTM software. Select GeneChip RTM output was validated by Quantitative RT-PCR. Relevance of a key gene, Growth arrest and DNA damage inducible (GADD45a), in the SIM2-s pathway was established. These results will provide a basis for the future experiments to understand the mechanism underlying Sim2-s activation in specific tumors.
Show less - Date Issued
- 2004
- PURL
- http://purl.flvc.org/fcla/dt/13146
- Subject Headings
- Medical informatics, DNA microarrays--Diagnostic use, Cancer--Genetic aspects, Apoptosis--Molecular aspects, Human genetics--Variation, Gene expression--Research--Methodology
- Format
- Document (PDF)
- Title
- Therapeutic potential of pomegranate and genistein for human breast cancer.
- Creator
- Louis Jeune, Marie Adeline, Florida Atlantic University, Kumi-Diaka, James
- Abstract/Description
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The therapeutic potential of pomegranate and genistein on growth inhibition of human breast cancer cells was investigated. Methods. Cells (MCF-7) were initially cultured for 48 hr to achieve 80% confluence; and then exposed to the agents in single and combination treatments. Post-treatment analysis was done by using a series of bioassays, including LDH, MTS, AcrO-EthBr, Annexin-FITC and TUNEL assays for growth inhibition and apoptosis detection; and Caspase-3 and NQO1 for molecular pathways...
Show moreThe therapeutic potential of pomegranate and genistein on growth inhibition of human breast cancer cells was investigated. Methods. Cells (MCF-7) were initially cultured for 48 hr to achieve 80% confluence; and then exposed to the agents in single and combination treatments. Post-treatment analysis was done by using a series of bioassays, including LDH, MTS, AcrO-EthBr, Annexin-FITC and TUNEL assays for growth inhibition and apoptosis detection; and Caspase-3 and NQO1 for molecular pathways of apoptosis. Results. Pomegranate and genistein showed significant dose- and time-dependent cytotoxic and growth inhibition effects as well as apoptosis induction in MCF-7 cancer cells, with significantly higher ( P < 0.01) effects in the combination treatments than in the single treatments. Both drugs induced apoptosis through a caspase-mediated mechanism and independent of NQO1. Discussion and conclusions. Pomegranate and genistein inhibit the growth of MCF-7 breast cancer cells through induction of apoptosis with combination treatment being more efficacious than single treatments.
Show less - Date Issued
- 2004
- PURL
- http://purl.flvc.org/fcla/dt/13130
- Subject Headings
- Phytochemicals--Physiological effect, Breast--Cancer--Molecular aspects, Women--Diseases--Alternative treatment, Apoptosis--Molecular aspects, Breast--Cancer--Treatment
- Format
- Document (PDF)
- Title
- Genistein targets only proliferating but not quiescent cells: Potential therapeutic significance in breast cancer.
- Creator
- Bodepudi, Sreedevi., Florida Atlantic University, Kumi-Diaka, James
- Abstract/Description
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Phytochemicals are biologically active secondary plant metabolites that could mimic biological activities. In this study genistein isoflavone, a phytochemical present in soy was investigated to determine its effect on the growth of human breast cancer cell line GI-101 and normal breast epithelial cells in vitro. The cells were exposed to varying concentrations of genistein isoflavone for 24 and 48 hour time periods and the effect was determined using post-treatment assays: MTT and Trypan Blue...
Show morePhytochemicals are biologically active secondary plant metabolites that could mimic biological activities. In this study genistein isoflavone, a phytochemical present in soy was investigated to determine its effect on the growth of human breast cancer cell line GI-101 and normal breast epithelial cells in vitro. The cells were exposed to varying concentrations of genistein isoflavone for 24 and 48 hour time periods and the effect was determined using post-treatment assays: MTT and Trypan Blue for cell viability; LDH assay for cytotoxicity; Rhodamine 123/Propidium Iodide and Ethidium Bromide/Acridine Orange assays for treatment-induced apoptosis and FAM Poly caspase assay for mechanism of action. The overall results revealed that genistein inhibited cell growth and proliferation through apoptosis in the cells in both time and dose-dependent manner. Normal breast epithelial cells were not significantly affected by genistein at the corresponding dosages. Based on the results obtained, it was concluded that genistein isoflavone could offer therapeutic efficacy in human breast carcinoma without significantly affecting the normal breast epithelial cells.
Show less - Date Issued
- 2006
- PURL
- http://purl.flvc.org/fcla/dt/13315
- Subject Headings
- Phytochemicals--Physiological effect, Breast--Cancer--Molecular aspects, Women--Diseases--Alternative treatment, Breast--Cancer--Treatment, Apoptosis--Molecular aspects
- Format
- Document (PDF)
- Title
- Mechanisms of protection against ischemic damage in the heart.
- Creator
- Moench, Ian, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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Heart disease including ischemic heart disease is the highest contributor to death and morbidity in the western world. The studies presented were conducted to determine possible pathways of protection of the heart against ischemia/reperfusion. We employed adenovirus mediated over-expression of Methionine sulfoxide reductase A (MsrA) in primary neonatal rat cardiac myocytes to determine the effect of this enzyme in protecting against hypoxia/reoxygenation. Cells transfected with MsrA encoding...
Show moreHeart disease including ischemic heart disease is the highest contributor to death and morbidity in the western world. The studies presented were conducted to determine possible pathways of protection of the heart against ischemia/reperfusion. We employed adenovirus mediated over-expression of Methionine sulfoxide reductase A (MsrA) in primary neonatal rat cardiac myocytes to determine the effect of this enzyme in protecting against hypoxia/reoxygenation. Cells transfected with MsrA encoding adenovirus and subjected to hypoxia/reoxygenation exhibited a 45% decrease in apoptosis as compared to controls. Likewise total cell death as determined by levels of Lactate Dehydrogenase (LDH) release was dramatically decreased by MsrA overexpression. The initial hypothesis that led to our testing sulindac was based on the fact that the S epimer of sulindac was a substrate for MsrA and that this compound might function as a catalytic anti-oxidant based on a reaction cycle that involved reductio n to sulindac sulfide followed by oxidation back to sulindac. To test this we examined the protective effect of sulindac in hypoxia re-oxygenation in both cardiac myocytes in culture and using a Langendorff model of myocardial ischemia. Using this model of myocardial ischemia we showed that pre-incubation of hearts with sulindac, or the S and R epimers of sulindac resulted in protection against cell death. We present several lines of evidence that the protective effect of sulindac is not dependent on the Msr enzyme system nor does it involve the well established role of sulindac as a Cyclooxygenase (COX) inhibitor. Numerous signaling pathways have been implicated in myocardial protective mechanisms, many of which require fluctuations in ROS levels as initiators or mediators., Sulindac shows very good potential as a preconditioning agent that could induce tissue protection against oxidative damage.Blocking of preconditioning pathways by administration of the PKC blocker chelerythine abrogated the ischemic protection afforded by sulindac. Secondly, an end-effector of preconditioning, inducible nitric oxide synthase (iNOS),was found to be induced by greater than 5 fold after 48 h prior feeding sulindac.
Show less - Date Issued
- 2008
- PURL
- http://purl.flvc.org/FAU/186291
- Subject Headings
- Biochemical markers, Diagnostic use, Cardiovascular system, Diseases, Diagnosis, Heart, Diseases, Molecular aspects, Medical care, Quality control, Coronary heart disease, Prevention, Apoptosis, Myocardial infarction, Prevention
- Format
- Document (PDF)