Modulation of Doxorubicin Intracellular Accumulation and Anticancer Activity by Triterpene Glycoside Cucumarioside A<sub>2</sub>-2
Ekaterina Menchinskaya,
Tatiana Gorpenchenko,
Alexandra Silchenko,
Sergey Avilov,
Dmitry Aminin
Affiliations
Ekaterina Menchinskaya
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
Tatiana Gorpenchenko
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
Alexandra Silchenko
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
Sergey Avilov
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
Dmitry Aminin
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
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.
