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- Title
- Discovery and investigation of survivin-targeting marine natural products from Ellisella paraplexauroides and Eudistoma olivaceum.
- Creator
- Francis, Kirstie Tandberg, Wright, Amy E., Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
In 2020, the National Institute of Health reported that more than 1.8 million people in the U.S. were diagnosed with cancer and over half a million died from those diseases. There is an urgent need for innovative and effective new treatments which stem from novel cancer drug targets. Survivin, the smallest member of the inhibitor of apoptosis protein (IAP) family, is highly expressed during development and in cancer cells but not in differentiated tissues, making it a tumor-selective target...
Show moreIn 2020, the National Institute of Health reported that more than 1.8 million people in the U.S. were diagnosed with cancer and over half a million died from those diseases. There is an urgent need for innovative and effective new treatments which stem from novel cancer drug targets. Survivin, the smallest member of the inhibitor of apoptosis protein (IAP) family, is highly expressed during development and in cancer cells but not in differentiated tissues, making it a tumor-selective target for new drug therapies. At only 16.5 kDa, it consists of a single Baculovirus IAP Repeat (BIR) domain and an α-helical coiled coil. Survivin plays a multitude of roles in the growth and survival of cancer cells—which can be attributed to the variable cellular localizations and posttranslational modifications of the protein—including inhibition of apoptosis, mitosis and cell cycle progression, DNA damage repair, drug resistance, metastasis, angiogenesis, and cell senescence, among others. A drug that is able to target surviving transcription or posttranslational modification or disrupt one of these critical pathways may serve as an attractive new cancer therapy. Despite decades of research on surviving and its intracellular functions, researchers have yet to find an FDA approved drug. Using a high throughput approach, Harbor Branch Oceanographic Institute’s chemical library of marine natural products was screened by the Guzmán lab to identify compounds capable of downregulating survivin expression in A549 non-small cell lung carcinoma and DLD-1 colorectal adenocarcinoma cell lines. From the screening assay, pure compounds were identified which reduce levels of survivin protein in cancer cells. Chapter 2 describes the isolation and structure elucidation of five polyhydroxylated sterol analogs from Ellisella paraplexauroides, four of them novel. Chapter 3 describes the isolation and structure elucidation of two compounds from Eudistoma olivaceum, eudistomin H and I. Chapter 4 describes the secondary biological testing employed to determine if the reduction of survivin expression was driven by reducing de novo production or increasing the degradation of existing protein by evaluating differential gene expression of survivin mRNA using reverse transcriptase quantitative polymerase chain reaction and measuring degradation rates of survivin protein, respectively.
Show less - Date Issued
- 2021
- PURL
- http://purl.flvc.org/fau/fd/FA00013828
- Subject Headings
- Survivin, Marine natural products, Antineoplastic agents--Development
- Format
- Document (PDF)
- Title
- Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells.
- Creator
- Guzman, Esther A., Maher, Michael, Temkin, Alexis, Pitts, Tara P., Wright, Amy E.
- Date Issued
- 2013-04-02
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000178
- Format
- Citation
- Title
- Correction: Kallifatidis, G. et al. The Marine Natural Product Manzamine A Targets Vacuolar ATPases and Inhibits Autophagy in Pancreatic Cancer Cells. Mar. Drugs 2013, 11, 3500–3516.
- Creator
- Kallifatidis, Georgios, Hoepfner, Dominic, Jaeg, Tiphaine, Guzman, Esther A., Wright, Amy E.
- Abstract/Description
-
We found two errors in our previous published paper [1]. Figure 4A has a mistake in the units in the labels, where it shows mM instead of micromolar (μM). A correctly labeled Figure 4A ensues. In Figures 2 and 4, the size bar scale is micrometers (μm). We apologize for the inconvenience caused to our readers.
- Date Issued
- 2014-04-21
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000076
- Format
- Citation
- Title
- The Marine Natural Product Manzamine A Targets Vacuolar ATPases and Inhibits Autophagy in Pancreatic Cancer Cells.
- Creator
- Kallifatidis, Georgios, Hoepfner, Dominic, Jaeg, Tiphaine, Guzman, Esther A., Wright, Amy E.
- Abstract/Description
-
Manzamine A, a member of the manzamine alkaloids, was originally isolated from marine sponges of the genus Haliclona. It was recently shown to have activity against pancreatic cancer cells, but the precise mechanism of action remained unclear. To further our understanding of the mechanism of action of manzamine A, chemogenomic profiling in the yeast S. cerevisiae was performed, suggesting that manzamine A is an uncoupler of vacuolar ATPases. Fluorescence microscopy confirmed this effect on...
Show moreManzamine A, a member of the manzamine alkaloids, was originally isolated from marine sponges of the genus Haliclona. It was recently shown to have activity against pancreatic cancer cells, but the precise mechanism of action remained unclear. To further our understanding of the mechanism of action of manzamine A, chemogenomic profiling in the yeast S. cerevisiae was performed, suggesting that manzamine A is an uncoupler of vacuolar ATPases. Fluorescence microscopy confirmed this effect on yeast vacuoles, where manzamine A produced a phenotype very similar to that of the established v-ATPase inhibitor bafilomycin A1. In pancreatic cancer cells, 10 μM manzamine A affected vacuolar ATPase activity and significantly increased the level of autophagosome marker LC3-II and p62/SQSTM1 as observed by western blot analysis. Treatment with manzamine A in combination with bafilomycin A1 (inhibitor of autophagosome-lysosome fusion) did not change the levels of LC3-II when compared to cells treated with bafilomycin A1 alone, suggesting that manzamine A is a potential inhibitor of autophagy by preventing autophagosome turnover. As autophagy is essential for pancreatic tumor growth, blocking this pathway with manzamine A suggests a promising strategy for the treatment of pancreatic cancer.
Show less - Date Issued
- 2013-09-17
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000075
- Format
- Citation
- Title
- Natural Products from the Lithistida: A Review of the Literature since 2000.
- Creator
- Winder, Priscilla L., Pomponi, Shirley A., Wright, Amy E.
- Abstract/Description
-
Lithistid sponges are known to produce a diverse array of compounds ranging from polyketides, cyclic and linear peptides, alkaloids, pigments, lipids, and sterols. A majority of these structurally complex compounds have very potent and interesting biological activities. It has been a decade since a thorough review has been published that summarizes the literature on the natural products reported from this amazing sponge order. This review provides an update on the current taxonomic...
Show moreLithistid sponges are known to produce a diverse array of compounds ranging from polyketides, cyclic and linear peptides, alkaloids, pigments, lipids, and sterols. A majority of these structurally complex compounds have very potent and interesting biological activities. It has been a decade since a thorough review has been published that summarizes the literature on the natural products reported from this amazing sponge order. This review provides an update on the current taxonomic classification of the Lithistida, describes structures and biological activities of 131 new natural products, and discusses highlights from the total syntheses of 16 compounds from marine sponges of the Order Lithistida providing a compilation of the literature since the last review published in 2002.
Show less - Date Issued
- 2011-12-15
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000059
- Format
- Citation
- Title
- Marine natural products.
- Creator
- Pomponi, Shirley A., Wright, Amy E., Reed, John K., McCarthy, Peter J.
- Date Issued
- 1999
- PURL
- http://purl.flvc.org/fau/fd/FA00007503
- Subject Headings
- Marine natural products
- Format
- Document (PDF)
- Title
- Total synthesis and biological evaluation of aseries of macrocyclic hybrids and analogues of the antimitotic natural products Dictyostatin,Discodermolide, and Taxol.
- Creator
- Paterson, Ian, Naylor, G. J., Gardner, Nicola M., Guzman, Esther A., Wright, Amy E.
- Date Issued
- 2011
- PURL
- http://purl.flvc.org/fau/fd/FA00007463
- Subject Headings
- Macrolides, Antimitotic Agents, Natural products, Tubulin
- Format
- Document (PDF)
- Title
- Leiodermatolide, a potent antimitotic macrolide from the marine sponge Leiodermatium sp.
- Creator
- Paterson, Ian, Dalby, S. M., Roberts, J. C., Naylor, G. J., Guzman, Esther A., Isbrucker, Richard A., Pitts, Tara P., Linley, P. A., Divlianska, D. B., Reed, John K., Wright, Amy E.
- Date Issued
- 2011
- PURL
- http://purl.flvc.org/fau/fd/FA00007465
- Subject Headings
- Antimitotic Agents, Macrolides, Sponges, Molecular structure, Nuclear Magnetic Resonance, Biomolecular, Cell lines
- Format
- Document (PDF)
- Title
- Isolation of marine natural products.
- Creator
- Wright, Amy E.
- Date Issued
- 1998
- PURL
- http://purl.flvc.org/fau/fd/FA00007419
- Subject Headings
- Marine natural products, Bioactive compounds--Biotechnology
- Format
- Document (PDF)
- Title
- Bioactivity of marine organisms: relationships with taxonomy, geography and depth.
- Creator
- Reed, John K., Sennett, Susan H., McCarthy, Peter J., Pitts, Tara P., Wright, Amy E., Pomponi, Shirley A.
- Date Issued
- 1998
- PURL
- http://purl.flvc.org/fau/fd/FA00007421
- Subject Headings
- Marine organisms, Bioactive compounds, Marine natural products
- Format
- Document (PDF)
- Title
- A new bicyclic guanidine alkaloid, Sch 575948, from amarine sponge, Ptilocaulis spiculifer.
- Creator
- Yang, Shu-Wei, Chan, Tze-Ming, Pomponi, Shirley A., Chen, Guodong, Wright, Amy E., Patel, Mahesh, Gullo, Vincent, Pramanik, B., Chu, Min
- Date Issued
- 2003
- PURL
- http://purl.flvc.org/fau/fd/FA00007361
- Subject Headings
- Sponges, Alkaloids, Guanidines, Antibacterial agents, Molecular structure
- Format
- Document (PDF)
- Title
- Cytotoxic peptides from marine sponges.
- Creator
- Gulavita, N. K., Wright, Amy E., McCarthy, Peter J., Pomponi, Shirley A., Longley, Ross E.
- Date Issued
- 1996
- PURL
- http://purl.flvc.org/fau/fd/FA00007341
- Subject Headings
- Sponges, Peptides, Cytotoxins, Stereochemistry
- Format
- Document (PDF)
- Title
- Development of techniques for in vitro production of bioactive natural products from marine sponges.
- Creator
- Pomponi, Shirley A., Willoughby, Robin, Kaighn, M. E., Wright, Amy E.
- Date Issued
- 1997
- PURL
- http://purl.flvc.org/fau/fd/FA00007344
- Subject Headings
- Sponges, Bioactive compounds, Marine natural products, Cell culture, Growth factors, Phytohemagglutinins, Cryopreservation
- Format
- Document (PDF)
- Title
- Antimicrobial constituent of the brown alga Sporochnus pedunculatus.
- Creator
- Gunasekera, L. S., Wright, Amy E., Gunasekera, Sarath P., McCarthy, Peter J., Reed, John K.
- Date Issued
- 1995
- PURL
- http://purl.flvc.org/fau/fd/FA00007231
- Subject Headings
- Brown algae, Antimicrobial agents, Nuclear magnetic resonance, Candida albicans, Bacillus subtilis
- Format
- Document (PDF)
- Title
- In vitro production of marine-derived antitumor compounds.
- Creator
- Pomponi, Shirley A., Willoughby, Robin, Wright, Amy E., Pecorella, C., Sennett, Susan H., Lopez, Jose V., Samples, Gail A.
- Date Issued
- 1998
- PURL
- http://purl.flvc.org/fau/fd/FA00007238
- Subject Headings
- Antineoplastic agents, Bioactive compounds, Marine natural products, In vitro, Antitumor agents
- Format
- Document (PDF)
- Title
- 1,1-Dimethyl-5,6-dihydroxyindolinium chloride from a deep water marine sponge, Dercitus sp.
- Creator
- Kohmoto, S., McConnell, O. J., Wright, Amy E.
- Date Issued
- 1988
- PURL
- http://purl.flvc.org/fau/fd/FA00007184
- Subject Headings
- Sponges, Marine metabolites, Chemical structure
- Format
- Document (PDF)
- Title
- Selective cytotoxic activity of the marine derivedbatzelline compounds against pancreatic cancer cell lines.
- Creator
- Guzman, Esther A., Johnson, J. D., Carrier, M. K., Meyer, C. I., Pitts, Tara P., Gunasekera, Sarath P., Wright, Amy E.
- Date Issued
- 2009
- PURL
- http://purl.flvc.org/fau/fd/FA00007114
- Subject Headings
- Pancreas--Cancer, Marine natural products, Drug Discovery, Sponges--Caribbean Sea, Mechanism of action (Biochemistry)
- Format
- Document (PDF)
- Title
- Total synthesis of a library of designed hybrids of the microtubule-stabilising anticancer agents taxol, discodermolide and dictyostatin.
- Creator
- Paterson, Ian, Naylor, G. J., Fujita, T., Guzman, Esther A., Wright, Amy E.
- Date Issued
- 2010
- PURL
- http://purl.flvc.org/fau/fd/FA00007065
- Subject Headings
- Antineoplastic agents, Paclitaxel, Polyketides, Microtubules, Tubulin Modulators, Marine natural products
- Format
- Document (PDF)
- Title
- Marine organisms as a source of novel lead structures for drug development.
- Creator
- Wright, Amy E.
- Date Issued
- 2000
- PURL
- http://purl.flvc.org/fau/fd/FA00007060
- Subject Headings
- Marine organisms, Marine natural products, Drug development
- Format
- Document (PDF)
- Title
- Stereochemical determination of dictyostatin, a novel microtubule-stabilising macrolide from the marine sponge Corallistidae sp.
- Creator
- Paterson, Ian, Britton, R., Delgado, Oscar, Wright, Amy E.
- Date Issued
- 2004
- PURL
- http://purl.flvc.org/fau/fd/FA00007061
- Subject Headings
- Macrolides, Sponges, Tubulin Modulators, Stereochemistry, Microtubules, Polyketides, Antimitotic Agents
- Format
- Document (PDF)