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Title: Potential mechanism of phytochemical-induced apoptosis in human prostate cancer cells: Genistein and beta-lapachone.
Creator: Saddler, Shawnette Simone, Florida Atlantic University, Kumi-Diaka, James
Abstract/Description: The present study was undertaken to determine the chemotherapeutic potential of genistein and beta-lapachone and possible mechanisms of action in prostate cancer in vitro. The bioassays used included: MTT and LDH chemosensitivity-cytotoxicity assays, NQO1 detection, annexin V-FITC, TUNEL and the caspase protease (CPP32) apoptotic detection assays. The results showed that: (i) PC3 cells are sensitive to single and combination treatments in a dose and time dependent manner; (ii) there was...
Show moreThe present study was undertaken to determine the chemotherapeutic potential of genistein and beta-lapachone and possible mechanisms of action in prostate cancer in vitro. The bioassays used included: MTT and LDH chemosensitivity-cytotoxicity assays, NQO1 detection, annexin V-FITC, TUNEL and the caspase protease (CPP32) apoptotic detection assays. The results showed that: (i) PC3 cells are sensitive to single and combination treatments in a dose and time dependent manner; (ii) there was treatment-induced dual death pathways (apoptosis and necrosis) with increasing toxicity (necrosis) at higher concentrations in single and combination treatments; (iii) combination treatment was more growth inhibitory than single treatments; (iv) the NQO1 enzyme substantially enhances the toxicity of beta-lapachone but not genistein, while genistein exerted its apoptotic inducing effects via the caspase 3 pathway. The overall results indicate that combination treatments with beta-lapachone and genistein are more efficacious in killing PC3 human prostate cancer cells than treatment with either agent alone.
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Date Issued: 2003
PURL: http://purl.flvc.org/fcla/dt/13042
Subject Headings: Prostate--Cancer--Cytopathology, Apoptosis, Prostate--Cancer--Molecular aspects
Format: Document (PDF)

Title: Synthesis, structural characterization and biological studies of organotin polyethers (Sn-O).
Creator: Barot, Girish Vallabhbhai., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Cancer is the second leading cause of death in the western world. In order to treat various types of cancer, platinum-based drugs are most widely employed as metal-containing chemotherapeutic agents. However, their clinical usage is hindered by toxic side effects, and by the emergence of drug resistance. Our focus was to replace platinum with less toxic metal like tin which can give better alternatives for cancer treatment. The major aim of our study was to synthesize novel organotin...
Show moreCancer is the second leading cause of death in the western world. In order to treat various types of cancer, platinum-based drugs are most widely employed as metal-containing chemotherapeutic agents. However, their clinical usage is hindered by toxic side effects, and by the emergence of drug resistance. Our focus was to replace platinum with less toxic metal like tin which can give better alternatives for cancer treatment. The major aim of our study was to synthesize novel organotin polyethers (Sn-O) which can be used to combat cancer. Preliminary results from our laboratory using organotin polyethers, that were synthesized by varying the structure of diols showed growth inhibition in Balb-3T3 cells. This study directly led us to hypothesize the two structural windows, first by changing the distance between diol and second, by presence of unsaturation in diols, the biological activity of organotin polyethers (Sn-O) can be enhanced significantly. Different series of polymeric compounds were synthesized based upon these two structural windows and the formation of products was validated using standard techniques like infrared spectroscopy (IR), light scattering photometer, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and nuclear magnetic resonance (NMR). The synthesized polymers arrested the growth of cancer cell lines including bone, prostate, colon, breast, pancreas and lung cancer derived cell lines in vitro. In number of instances where chemotherapeutic index values of two and greater were found that these polymers are significantly more active against cancer cells than non-cancerous cells in culture., These results support the starting premise that the polymers may exhibit cancer cell selectivity. In general, it was found that the presence of unsaturation increased the probability that the polyether would inhibit the growth of various cancer cell lines. Further, in some cases, polyethers with short distances between the oxygen atoms showed a superior ability to inhibit the growth of various cancer cell lines in comparison to those with longer distances between the oxygen atoms. These results provide a framework for the discovery of novel cancer therapeutics.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/186672
Subject Headings: Organometallic polymers, Cancer, Molecular aspects, Apoptosis, Molecular aspects, Antineoplastic agents, Testing, Polymers in medicine
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.
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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: 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.
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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: 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.
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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: Correlation between specific carcinogenic chemicals and specific mitotic defects and the restorative role of antioxidants.
Creator: Yates, Travis., Harriet L. Wilkes Honors College
Abstract/Description: The progression of cancerous cells towards a more aggressive tumor can be linked to external elements called carcinogens. The goal of this project is to examine the correlation between exposure to specific carcinogens and an increase of mitotic defects. These defects can manifest as lagging chromosomes, multipolar spindles, and anaphase bridges. Some of these instabilities are associated with the formation of reactive oxygen species (ROS), which are known to damage DNA. The potential for...
Show moreThe progression of cancerous cells towards a more aggressive tumor can be linked to external elements called carcinogens. The goal of this project is to examine the correlation between exposure to specific carcinogens and an increase of mitotic defects. These defects can manifest as lagging chromosomes, multipolar spindles, and anaphase bridges. Some of these instabilities are associated with the formation of reactive oxygen species (ROS), which are known to damage DNA. The potential for damage to the genome can be averted via antioxidants. Using the oral cancer cell line UPCI:SCC103, we established a baseline for the mitotic defects in the absence and presence of various ROS-inducing carcinogens using DAPI-stained fixed cells examined by immunofluorescent microscopy, The cells were treated with varying concentrations of the antioxidants, Vitamin C, (Sb(B-Carotene, and Vitamin E. The reactive oxygen scavengers significantly reduced the number of mitotic defects. A possible link between the carcinogens and lagging chromosomes was established.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/210007
Subject Headings: Cellular signal transduction, Genetic regulation, Antioxidants, Therapeutic use, Apoptosis, Molecular aspects, Cancer, Chemoprevention
Format: Document (PDF)

Title: Gene selection for sample sets with biased distribution.
Creator: Kamal, Abu Hena Mustafa., College of Engineering and Computer Science, Department of Computer and Electrical Engineering and Computer Science
Abstract/Description: Microarray expression data which contains the expression levels of a large number of simultaneously observed genes have been used in many scientific research and clinical studies. Due to its high dimensionalities, selecting a small number of genes has shown to be beneficial for many tasks such as building prediction models from the microarray expression data or gene regulatory network discovery. Traditional gene selection methods, however, fail to take the class distribution into the...
Show moreMicroarray expression data which contains the expression levels of a large number of simultaneously observed genes have been used in many scientific research and clinical studies. Due to its high dimensionalities, selecting a small number of genes has shown to be beneficial for many tasks such as building prediction models from the microarray expression data or gene regulatory network discovery. Traditional gene selection methods, however, fail to take the class distribution into the selection process. In biomedical science, it is very common to have microarray expression data which is severely biased with one class of examples (e.g., diseased samples) significantly less than other classes (e.g., normal samples). These sample sets with biased distributions require special attention from researchers for identification of genes responsible for a particular disease. In this thesis, we propose three filtering techniques, Higher Weight ReliefF, ReliefF with Differential Minority Repeat and ReliefF with Balanced Minority Repeat to identify genes responsible for fatal diseases from biased microarray expression data. Our solutions are evaluated on five well-known microarray datasets, Colon, Central Nervous System, DLBCL Tumor, Lymphoma and ECML Pancreas. Experimental comparisons with the traditional ReliefF filtering method demonstrate the effectiveness of the proposed methods in selecting informative genes from microarray expression data with biased sample distributions.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/186330
Subject Headings: Gene expression, Research, Methodology, Medical informatics, Apoptosis, Molecular aspects, DNA microarrays, Research
Format: Document (PDF)

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: 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.
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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: 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.
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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.
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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: 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.
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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: 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.
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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: 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: 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.
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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
Format: 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: 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.
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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: Therapeutic potential of pomegranate and genistein for human breast cancer.
Creator: Louis Jeune, Marie Adeline, Florida Atlantic University, Kumi-Diaka, James
Abstract/Description: 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.
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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: 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.
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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: 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.
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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: 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: 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.
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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: Molecular pathway identification using microarray technology.
Creator: Tress, Matthew David., Florida Atlantic University, Narayanan, Ramaswamy
Abstract/Description: 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.
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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: Analysis of the Role of Autophagy in Dauer Formation and Dauer Recovery Regulated by TGF-β Signaling Pathway in Caenorhabditis elegans.
Creator: Ritter, Portia, Jia, Kailiang, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Caenorhabditis elegans optionally enter into a dauer diapause phase that results in a prolonged life in a semi-dormant state. Entry into and recovery from dauer diapause includes many physical changes in body structure, physiology, and gene expression. Entry into dauer diapause is regulated by several signaling pathways including transforming growth factor (TGF-β). Autophagy plays an important role in dauer formation and recover. During dauer transformation autophagy is up-regulated and may...
Show moreCaenorhabditis elegans optionally enter into a dauer diapause phase that results in a prolonged life in a semi-dormant state. Entry into and recovery from dauer diapause includes many physical changes in body structure, physiology, and gene expression. Entry into dauer diapause is regulated by several signaling pathways including transforming growth factor (TGF-β). Autophagy plays an important role in dauer formation and recover. During dauer transformation autophagy is up-regulated and may play a role in remodeling the molecular structure for long term survival during dauer diapause. This research helps determine the role of autophagy in dauer development and recovery mediated through the TGF-β signaling pathway. This research also determines in which tissue autophagy is necessary for dauer formation and recovery through TGF-β signaling. This research is shedding light on the function of autophagy in the TGF-β signaling pathway, both processes of which have been linked to tumorigenesis, heart disease and cancer.
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Date Issued: 2017
PURL: http://purl.flvc.org/fau/fd/FA00004921, http://purl.flvc.org/fau/fd/FA00004921
Subject Headings: Aging--Molecular aspects., Aging--Physiological aspects., Caenorhabditis elegans--Molecular genetics., Autophagic vacuoles., Gene expression., Apoptosis., Cellular signal transduction., DNA-binding proteins., Transforming growth factors-beta--Receptors.
Format: Document (PDF)

FAU Theses and Dissertations (20)	+ -
Honors Student Theses (2)	+ -

Apoptosis (9)	+ -
Apoptosis--Molecular aspects (8)	+ -
Molecular aspects (7)	+ -
Cancer (5)	+ -
Cellular signal transduction (5)	+ -

Phytochemicals--Physiological effect (5)	+ -
Antioxidants (3)	+ -
Apoptosis. (3)	+ -
Breast--Cancer--Treatment (3)	+ -
Medical informatics (3)	+ -
Therapeutic use (3)	+ -
Adjuvant treatment (2)	+ -
Aging--Molecular aspects. (2)	+ -
Apoptosis -- Molecular aspects (2)	+ -
Autophagic vacuoles. (2)	+ -
Breast--Cancer--Molecular aspects (2)	+ -
Caenorhabditis elegans--Molecular genetics. (2)	+ -
Cancer--Genetic aspects (2)	+ -
Cell death. (2)	+ -
Cellular signal transduction. (2)	+ -
Chemoprevention (2)	+ -
DNA microarrays--Diagnostic use (2)	+ -
Gene expression--Research--Methodology (2)	+ -
Gene expression. (2)	+ -
Genetic regulation (2)	+ -
Physiological effect (2)	+ -
Phytochemicals (2)	+ -
Phytochemicals -- Physiological effect (2)	+ -
Phytochemicals -- Therapeutic use (2)	+ -
Polymers in medicine (2)	+ -

Electronic Thesis or Dissertation (20)	+ -
thesis (2)	+ -

Florida Atlantic University (15)	+ -
Charles E. Schmidt College of Science (10)	+ -
Department of Biological Sciences (9)	+ -
Kumi-Diaka, James (9)	+ -
Harriet L. Wilkes Honors College (2)	+ -

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