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Modulation of Doxorubicin Intracellular Accumulation and Anticancer Activity by Triterpene Glycoside Cucumarioside A2-2

1
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100-letya Vladivostoka, 159, 690022 Vladivostok, Russia
2
Federal Scientific Center of the East Asia Terrestrial Biodiversity, Far-Eastern Branch of the Russian Academy of Science, Prospect 100-letya Vladivostoka, 159, 690022 Vladivostok, Russia
3
Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan
*
Author to whom correspondence should be addressed.
Mar. Drugs 2019, 17(11), 597; https://doi.org/10.3390/md17110597
Received: 27 August 2019 / Revised: 21 October 2019 / Accepted: 21 October 2019 / Published: 23 October 2019
(This article belongs to the Special Issue Active Compounds from Sea Cucumber)
The effect of treatment of Ehrlich ascites carcinoma (EAC) cells with multidrug resistance by holothurian triterpene glycoside, cucumarioside A2-2 (CA2-2) was evaluated. Calcein-AM efflux assay and doxorubicin (DOX) uptake and retention measurement in cancer cells, as well as determination of DOX cytotoxic and anticancer effects were applied. Treatment of EAC cells with CA2-2 (0.01–0.1 μM) blocked Calcein-AM and DOX efflux from cancer cells and increased the accumulation and cytotoxicity of DOX in EAC cells. Moreover, pre-treatment of mice with EAC by CA2-2 (10 μg/kg/5 days, intraperitoneal injection (i.p.)), then transplantation of tumor cells into fresh animals and subsequent treatment of these mice with DOX (2 mg/kg/3 days i.p.) significantly increased average life span (ALS) of mice bearing a tumor and therefore boosted the antitumor effect of doxorubicin in vivo. View Full-Text
Keywords: cucumarioside A2-2; doxorubicin; ehrlich ascites carcinoma; MDR; sea cucumbers; triterpene glycosides cucumarioside A2-2; doxorubicin; ehrlich ascites carcinoma; MDR; sea cucumbers; triterpene glycosides
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Menchinskaya, E.; Gorpenchenko, T.; Silchenko, A.; Avilov, S.; Aminin, D. Modulation of Doxorubicin Intracellular Accumulation and Anticancer Activity by Triterpene Glycoside Cucumarioside A2-2. Mar. Drugs 2019, 17, 597.

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