The molecular pharmacology of symplostatin 1: A new antimitotic dolastatin 10 analog
Open accessAbstract
Symplostatin 1, an analog of dolastatin 10, was recently isolated from cyanobacteria of the genus Symploca. Symplostatin 1 is a potent inhibitor of cell proliferation with IC 50 values in the low nanomolar range and it exhibits efficacy against a variety of cancer cell types. Symplostatin 1 caused the formation of abnormal mitotic spindles and accumulation of cells in metaphase at concentrations that had only minor effects on interphase microtubules. At higher concentrations, symplostatin 1 caused the loss of interphase microtubules. Cell cycle analysis revealed that symplostatin 1 caused G 2/M arrest, consistent with its effects on mitotic spindles. Symplostatin 1 initiated the phosphorylation of Bcl‐2, formation of micronuclei and activation of caspase 3, indicating induction of apoptosis. The cellular effects of symplostatin 1 are consistent with other antimitotic tubulin‐targeting drugs. Tubulin polymerization experiments indicated that symplostatin 1 potently inhibits the assembly of purified tubulin, suggesting that tubulin may be its intracellular target. Some microtubule‐targeting agents are reported to have antiangiogenic activity and therefore the effects of symplostatin 1 on endothelial cell proliferation and invasion were evaluated. Symplostatin 1 was found to be a potent inhibitor of both endothelial cell proliferation and invasion. Because of its potent and broad activity in vitro, symplostatin 1 was evaluated in vivo. Symplostatin 1 was active against murine colon 38 and murine mammary 16/C; however, it was poorly tolerated and the mice were slow to recover from the toxicity. The data indicate that symplostatin 1 has a mechanism of action similar to dolastatin 10. © 2003 Wiley‐Liss, Inc.
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Dolastatin 10 and symplostatin 1 exhibit cytotoxic effects against human lung and breast cancer cell lines via Bcl-2 phosphorylation and caspase-3 protein activation.
“The linear pentapeptides dolastatin 10 and symplostatin 1 were isolated from Symploca spp. and exhibited cytotoxic effects against human lung and breast cancer cell lines, via both Bcl-2 phosphorylation and caspase-3 protein activation [183,184].”
From Marine Natural Products: A Source of Novel Anticancer Drugs (2019) · cites this paper as [183]
The Cell culture section identifies MDA-MB-435 as a human breast cancer cell line, and the Bcl-2 phosphorylation and Symplostatin 1-induced caspase 3 activation sections report those effects after symplostatin 1 treatment. The paper does not establish the same pathway for dolastatin 10 or report these effects in a human lung cancer cell line. Its isolation statement specifically concerns symplostatin 1, not both peptides. (LLM, conf=0.88)
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“and exhibited cytotoxic effects against human lung and breast cancer cell lines, via both Bcl-2 phosphorylation and caspase-3 protein activation [183,184].”
BackgroundMicroalgae in modern cancer therapy: current knowledge
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- Authors
- Mooberry, S. L., Leal, R. M., Tinley, T. L., Luesch, H., Moore, R. E., & Corbett, T. H.
- Affiliations
- Texas Biomedical Research Institute (US)
- University of Hawaiʻi at Mānoa (US)
- Wayne State University (US)
- Corresponding author
- Mooberry, Susan L.
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2003-01-21
- Volume
- 104
- Issue
- 4
- Pages
- 512-521
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2085051374
- Cited by
- 87
- References
- 47
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 8 · 2022: 4 · 2021: 8 · 2020: 14 · 2019: 5 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 5 · 2014: 1 · 2013: 4 · 2012: 2
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca012623-29, 5r29ca070743-06)
- National Cancer Institute (CA12623, CA70743, CA-53001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- antimitotic agents, tubulin polymerization inhibition, microtubule inhibitors, mitotic spindle defects, G2/M cell cycle arrest, apoptosis, Bcl-2 phosphorylation, caspase-3, micronuclei, antiangiogenic activity, endothelial cell proliferation, endothelial cell invasion, anticancer natural products, colon cancer, breast cancer, drug toxicity
- MeSH terms
- Animals, Antineoplastic Agents, Cell Nucleus, Cells, Cultured, Endothelium, Vascular, Humans, Interphase, Mice, Inbred C57BL, Microtubules, Mitosis, Spindle Apparatus, Neoplasms, Experimental, Oligopeptides, Phosphorylation, Tubulin, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-bcl-2, Caspases, Depsipeptides, Mice, Rats, Caspase 3
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