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Mar Drugs. 2015 Mar 6;13(3):1202-23. doi: 10.3390/md13031202.

Anticancer activity of sea cucumber triterpene glycosides.

Author information

1
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 letya Vladivostoka, 159, Vladivostok 690022, Russia. d_aminin@hotmail.com.
2
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 letya Vladivostoka, 159, Vladivostok 690022, Russia. ekaterinamenchinskaya@gmail.com.
3
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 letya Vladivostoka, 159, Vladivostok 690022, Russia. pislyagin@hotmail.com.
4
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 letya Vladivostoka, 159, Vladivostok 690022, Russia. sialexandra@mail.ru.
5
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 letya Vladivostoka, 159, Vladivostok 690022, Russia. avilov-1957@mail.ru.
6
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 letya Vladivostoka, 159, Vladivostok 690022, Russia. kalininv@piboc.dvo.ru.

Abstract

Triterpene glycosides are characteristic secondary metabolites of sea cucumbers (Holothurioidea, Echinodermata). They have hemolytic, cytotoxic, antifungal, and other biological activities caused by membranotropic action. These natural products suppress the proliferation of various human tumor cell lines in vitro and, more importantly, intraperitoneal administration in rodents of solutions of some sea cucumber triterpene glycosides significantly reduces both tumor burden and metastasis. The anticancer molecular mechanisms include the induction of tumor cell apoptosis through the activation of intracellular caspase cell death pathways, arrest of the cell cycle at S or G2/M phases, influence on nuclear factors, NF-κB, and up-down regulation of certain cellular receptors and enzymes participating in cancerogenesis, such as EGFR (epidermal growth factor receptor), Akt (protein kinase B), ERK (extracellular signal-regulated kinases), FAK (focal adhesion kinase), MMP-9 (matrix metalloproteinase-9) and others. Administration of some glycosides leads to a reduction of cancer cell adhesion, suppression of cell migration and tube formation in those cells, suppression of angiogenesis, inhibition of cell proliferation, colony formation and tumor invasion. As a result, marked growth inhibition of tumors occurs in vitro and in vivo. Some holothurian triterpene glycosides have the potential to be used as P-gp mediated MDR reversal agents in combined therapy with standard cytostatics.

PMID:
25756523
PMCID:
PMC4377980
DOI:
10.3390/md13031202
[Indexed for MEDLINE]
Free PMC Article

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