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Published on: June 26, 2018
Antitumor activity of cucumarioside A2-2
E S Menchinskaya1, E A Pislyagin, S N Kovalchyk
1G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far East Division of the Russian Academy of Sciences, Vladivostok, Russia.
Background:
The cytotoxic activity of sea cucumber glycosides against different types of cells and cell lines, including human tumor cell lines, has been studied for many years. However, the molecular mechanism(s) of the antitumor action of triterpene glycosides on cancer cells remain unclear. This article reports a continuation of investigations of triterpene glycoside cucumarioside A2-2 isolated from the Far-Eastern sea cucumber Cucumaria japonica. It describes a study of glycoside anticancer activity in vivo and glycoside interaction with mouse Ehrlich carcinoma cells in vitro.
Methods:
The cytotoxicity of cucumarioside A2-2 and its effect on apoptosis, the cell cycle, DNA biosynthesis and p53 activity, and glycoside anticancer action against Ehrlich carcinoma cells were studied.
Results:
Cucumarioside A2-2 influences tumor cell viability at micromolar concentrations. The EC50 for glycoside estimated by nonspecific esterase assay and MTT assay was 2.1 and 2.7 μM, respectively. Cucumarioside A2-2 at a subcytotoxic range of concentrations exhibits a cytostatic effect by blocking cell proliferation and DNA biosynthesis in the S phase. It may induce apoptosis in tumor cells in a caspase-dependent way, bypassing the activation of the p53-dependent segment.
Conclusion:
The anticancer and proapoptotic properties of cucumarioside A2-2 may be due to direct interaction of the glycoside with tumor cells. The in vivo anticancer effect of cucumarioside A2-2 may be associated with the ability of the drug to arrest the cell cycle in the synthetic phase and induce programmed tumor cell death.
Insights
Sea cucumber glycoside cucumarioside A2-2 shows anticancer effects by stopping cancer cell growth and causing programmed cell death. This study clarifies its molecular mechanisms against Ehrlich carcinoma cells.
Area of Science:
- Marine natural products
- Pharmacology
- Cancer biology
Background:
- Sea cucumber glycosides exhibit cytotoxic activity against various cells, including human tumor cell lines.
- The precise molecular mechanisms underlying the antitumor effects of triterpene glycosides on cancer cells require further elucidation.
- This study investigates cucumarioside A2-2, a triterpene glycoside from Cucumaria japonica, focusing on its anticancer properties.
Purpose of the Study:
- To investigate the in vivo anticancer activity of cucumarioside A2-2.
- To explore the interaction of cucumarioside A2-2 with mouse Ehrlich carcinoma cells in vitro.
- To elucidate the molecular mechanisms of cucumarioside A2-2's antitumor effects.
Main Methods:
- Cytotoxicity assessment using MTT and nonspecific esterase assays.
- Analysis of apoptosis, cell cycle, DNA biosynthesis, and p53 activity.
- In vitro and in vivo studies on Ehrlich carcinoma cells.
Main Results:
- Cucumarioside A2-2 demonstrated significant cytotoxicity against tumor cells at micromolar concentrations (EC50 values of 2.1–2.7 μM).
- At subcytotoxic concentrations, it induced a cytostatic effect, arresting cell proliferation and DNA biosynthesis in the S phase.
- Apoptosis was induced in a caspase-dependent manner, independent of p53 activation.
Conclusions:
- Cucumarioside A2-2 possesses anticancer and proapoptotic properties, likely through direct interaction with tumor cells.
- The in vivo anticancer effects are attributed to cell cycle arrest in the synthetic phase and induction of programmed cell death.
- This glycoside represents a potential therapeutic agent for cancer treatment.
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