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Discovery and investigation of survivin-targeting marine natural products from Ellisella paraplexauroides and Eudistoma olivaceum
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.
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Date Issued
2021
PURL
http://purl.flvc.org/fau/fd/FA00013828
Subject Headings
Survivin, Marine natural products, Antineoplastic agents--Development
Format
Document (PDF)
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
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
The Marine Natural Product Manzamine A Targets Vacuolar ATPases and Inhibits Autophagy in Pancreatic Cancer Cells
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.
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Date Issued
2013-09-17
PURL
http://purl.flvc.org/fau/fd/FAUIR000075
Format
Citation
Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells
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
Natural Products from the Lithistida: A Review of the Literature since 2000
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.
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Date Issued
2011-12-15
PURL
http://purl.flvc.org/fau/fd/FAUIR000059
Format
Citation
Leiodermatolide, a potent antimitotic macrolide from the marine sponge Leiodermatium sp.
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)
Total synthesis and biological evaluation of aseries of macrocyclic hybrids and analogues of the antimitotic natural products Dictyostatin,Discodermolide, and Taxol
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)
A novel activity from an old compound: Manzamine A reduces the metastatic potential of AsPC-1 pancreatic cancer cells and sensitizes them to TRAIL-induced apoptosis
Title
A novel activity from an old compound: Manzamine A reduces the metastatic potential of AsPC-1 pancreatic cancer cells and sensitizes them to TRAIL-induced apoptosis.
Creator
Guzman, Esther A., Johnson, J. D., Linley, P. A., Wright, Amy E., Gunasekera, Sarath P.
Date Issued
2010
PURL
http://purl.flvc.org/FCLA/DT/3318907
Subject Headings
Pancreas--Cancer, Apoptosis, Sponges--Research, Marine natural products, Drug Discovery
Format
Document (PDF)
Total synthesis of a library of designed hybrids of the microtubule-stabilising anticancer agents taxol, discodermolide and dictyostatin
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)
Gymnochromes E and F, cytotoxic phenanthroperylenequinones from a deep-water crinoid, Holopus rangii
Title
Gymnochromes E and F, cytotoxic phenanthroperylenequinones from a deep-water crinoid, Holopus rangii.
Creator
Wangun, H. V. K., Wood, A., Fiorilla, C., Reed, John K., McCarthy, Peter J., Wright, Amy E.
Date Issued
2010
PURL
http://purl.flvc.org/FCLA/DT/3319112
Subject Headings
Crinoidea, Marine natural products, Cytotoxin, Marine metabolites, Anthraquinones
Format
Document (PDF)
The Lithistida: important sources of compounds useful in biomedical research
Title
The Lithistida: important sources of compounds useful in biomedical research.
Creator
Wright, Amy E.
Date Issued
2010
PURL
http://purl.flvc.org/FCLA/DT/3331940
Subject Headings
Sponges, Biomedical research, Marine natural products, Bioactive compounds
Format
Document (PDF)
Total synthesis and biological evaluation of novel C2–C6 region analogues of dictyostatin
Title
Total synthesis and biological evaluation of novel C2–C6 region analogues of dictyostatin.
Creator
Paterson, Ian, Gardner, Nicola M., Guzman, Esther A., Wright, Amy E.
Date Issued
2009-03-15
PURL
http://purl.flvc.org/FCLA/DT/1745595
Subject Headings
Bioorganic chemistry, Cancer--Research
Format
Document (PDF)
Isolation, synthesis, and biological activity of Aphrocallistin, an adenine-substituted bromotyramine metabolite from the hexactinellida sponge Aphrocallistes beatrix
Title
Isolation, synthesis, and biological activity of Aphrocallistin, an adenine-substituted bromotyramine metabolite from the hexactinellida sponge Aphrocallistes beatrix.
Creator
Wright, Amy E., Roth, G. P., Hoffman, J. K., Divlianska, D. B., Pechter, D., Sennett, Susan H., Guzman, Esther A., Linley, P. A., McCarthy, Peter J., Pitts, Tara P., Pomponi, Shirley A., Reed, John K.
Date Issued
2009
PURL
http://purl.flvc.org/FCLA/DT/3319109
Subject Headings
Sponges --Research, Marine metabolites, Marine natural products, Hexactinellida
Format
Document (PDF)
Selective cytotoxic activity of the marine derivedbatzelline compounds against pancreatic cancer cell lines
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)
Total synthesis and biological evaluation of potent analogues of dictyostatin: modification of the C2-C6 dienoate region
Title
Total synthesis and biological evaluation of potent analogues of dictyostatin: modification of the C2-C6 dienoate region.
Creator
Paterson, Ian, Gardner, Nicola M., Guzman, Esther A., Wright, Amy E.
Date Issued
2008-12-01
PURL
http://purl.flvc.org/FCLA/DT/1591053
Subject Headings
Bioorganic chemistry, Cancer--Research
Format
Document (PDF)
Use of real-time qPCR to quantify members of the unculturable heterotrophic bacterial community in a deep sea marine sponge, Vetulina sp
Title
Use of real-time qPCR to quantify members of the unculturable heterotrophic bacterial community in a deep sea marine sponge, Vetulina sp.
Creator
Cassler, M., Peterson, C. L., Ledger, Angela, Pomponi, Shirley A., Wright, Amy E., Winegar, R., McCarthy, Peter J., Lopez, Jose V.
Date Issued
2008
PURL
http://purl.flvc.org/FCLA/DT/2708323
Subject Headings
Microbiology --Research, Sponges --Microbiology, Marine biology --Caribbean Area
Format
Document (PDF)
Total synthesis of a potent hybrid of the anticancer natural products dictyostatin and discodermolide.
Title
Total synthesis of a potent hybrid of the anticancer natural products dictyostatin and discodermolide.
Creator
Paterson, Ian, Naylor, G. J., Wright, Amy E.
Date Issued
2008
PURL
http://purl.flvc.org/fau/fd/FA00007062
Subject Headings
Antineoplastic agents, Macrolides, Polyketides, Tubulin Modulators, Marine natural products, Sponges
Format
Document (PDF)
Synthesis and biological evaluation of 10, 11-Dihydrodictyostatin, a potent analogue of the marine anticancer agent dictyostatin
Title
Synthesis and biological evaluation of 10, 11-Dihydrodictyostatin, a potent analogue of the marine anticancer agent dictyostatin.
Creator
Paterson, Ian, Gardner, Nicola M., Poullennec, Karine G., Wright, Amy E.
Date Issued
2008
PURL
http://purl.flvc.org/FCLA/DT/3333013
Subject Headings
Macrolides, Antineoplastic agents, Biological evaluation, Synthesis, Antimitotic agents
Format
Document (PDF)
Neopeltolide a new macrolide from a lithistid sponge of the family Neopeltidae
Title
Neopeltolide a new macrolide from a lithistid sponge of the family Neopeltidae.
Creator
Wright, Amy E., Botelho, J. C., Guzman, Esther A., Harmody, Dedra K., Linley, P. A., McCarthy, Peter J., Pitts, Tara P., Pomponi, Shirley A., Reed, John K.
Date Issued
2007
PURL
http://purl.flvc.org/FCLA/DT/3333011
Subject Headings
Sponges, Macrolides, Marine natural products
Format
Document (PDF)
Synthesis and biological evaluation of novel analogues of dictyostatin
Title
Synthesis and biological evaluation of novel analogues of dictyostatin.
Creator
Paterson, Ian, Gardner, Nicola M., Poullennec, Karine G., Wright, Amy E.
Date Issued
2007
PURL
http://purl.flvc.org/FCLA/DT/2763290
Subject Headings
Microtubules --Research--Methodology, Microtubules
Format
Document (PDF)

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