Modulation of Doxorubicin Intracellular Accumulation and Anticancer Activity by Triterpene Glycoside Cucumarioside A<sub>2</sub>-2

The effect of treatment of Ehrlich ascites carcinoma (EAC) cells with multidrug resistance by holothurian triterpene glycoside, cucumarioside A<sub>2</sub>-2 (CA<sub>2</sub>-2) was evaluated. Calcein-AM efflux assay and doxorubicin (DOX) uptake and retention measurement in ca...

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Main Authors: Ekaterina Menchinskaya, Tatiana Gorpenchenko, Alexandra Silchenko, Sergey Avilov, Dmitry Aminin
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Marine Drugs
Subjects:
Online Access:https://www.mdpi.com/1660-3397/17/11/597
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author Ekaterina Menchinskaya
Tatiana Gorpenchenko
Alexandra Silchenko
Sergey Avilov
Dmitry Aminin
author_facet Ekaterina Menchinskaya
Tatiana Gorpenchenko
Alexandra Silchenko
Sergey Avilov
Dmitry Aminin
author_sort Ekaterina Menchinskaya
collection DOAJ
description The effect of treatment of Ehrlich ascites carcinoma (EAC) cells with multidrug resistance by holothurian triterpene glycoside, cucumarioside A<sub>2</sub>-2 (CA<sub>2</sub>-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 CA<sub>2</sub>-2 (0.01&#8722;0.1 &#956;M) 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 CA<sub>2</sub>-2 (10 &#956;g/kg/5 days, intraperitoneal injection (<i>i.p.</i>)), then transplantation of tumor cells into fresh animals and subsequent treatment of these mice with DOX (2 mg/kg/3 days <i>i.p.</i>) significantly increased average life span (ALS) of mice bearing a tumor and therefore boosted the antitumor effect of doxorubicin in vivo.
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spelling doaj.art-4de641e277d04abeb078daf42c5975282022-12-22T04:10:23ZengMDPI AGMarine Drugs1660-33972019-10-01171159710.3390/md17110597md17110597Modulation of Doxorubicin Intracellular Accumulation and Anticancer Activity by Triterpene Glycoside Cucumarioside A<sub>2</sub>-2Ekaterina Menchinskaya0Tatiana Gorpenchenko1Alexandra Silchenko2Sergey Avilov3Dmitry Aminin4G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100-letya Vladivostoka, 159, 690022 Vladivostok, RussiaFederal Scientific Center of the East Asia Terrestrial Biodiversity, Far-Eastern Branch of the Russian Academy of Science, Prospect 100-letya Vladivostoka, 159, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100-letya Vladivostoka, 159, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100-letya Vladivostoka, 159, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100-letya Vladivostoka, 159, 690022 Vladivostok, RussiaThe effect of treatment of Ehrlich ascites carcinoma (EAC) cells with multidrug resistance by holothurian triterpene glycoside, cucumarioside A<sub>2</sub>-2 (CA<sub>2</sub>-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 CA<sub>2</sub>-2 (0.01&#8722;0.1 &#956;M) 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 CA<sub>2</sub>-2 (10 &#956;g/kg/5 days, intraperitoneal injection (<i>i.p.</i>)), then transplantation of tumor cells into fresh animals and subsequent treatment of these mice with DOX (2 mg/kg/3 days <i>i.p.</i>) significantly increased average life span (ALS) of mice bearing a tumor and therefore boosted the antitumor effect of doxorubicin in vivo.https://www.mdpi.com/1660-3397/17/11/597cucumarioside a<sub>2</sub>-2doxorubicinehrlich ascites carcinomamdrsea cucumberstriterpene glycosides
spellingShingle Ekaterina Menchinskaya
Tatiana Gorpenchenko
Alexandra Silchenko
Sergey Avilov
Dmitry Aminin
Modulation of Doxorubicin Intracellular Accumulation and Anticancer Activity by Triterpene Glycoside Cucumarioside A<sub>2</sub>-2
Marine Drugs
cucumarioside a<sub>2</sub>-2
doxorubicin
ehrlich ascites carcinoma
mdr
sea cucumbers
triterpene glycosides
title Modulation of Doxorubicin Intracellular Accumulation and Anticancer Activity by Triterpene Glycoside Cucumarioside A<sub>2</sub>-2
title_full Modulation of Doxorubicin Intracellular Accumulation and Anticancer Activity by Triterpene Glycoside Cucumarioside A<sub>2</sub>-2
title_fullStr Modulation of Doxorubicin Intracellular Accumulation and Anticancer Activity by Triterpene Glycoside Cucumarioside A<sub>2</sub>-2
title_full_unstemmed Modulation of Doxorubicin Intracellular Accumulation and Anticancer Activity by Triterpene Glycoside Cucumarioside A<sub>2</sub>-2
title_short Modulation of Doxorubicin Intracellular Accumulation and Anticancer Activity by Triterpene Glycoside Cucumarioside A<sub>2</sub>-2
title_sort modulation of doxorubicin intracellular accumulation and anticancer activity by triterpene glycoside cucumarioside a sub 2 sub 2
topic cucumarioside a<sub>2</sub>-2
doxorubicin
ehrlich ascites carcinoma
mdr
sea cucumbers
triterpene glycosides
url https://www.mdpi.com/1660-3397/17/11/597
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AT tatianagorpenchenko modulationofdoxorubicinintracellularaccumulationandanticanceractivitybytriterpeneglycosidecucumariosideasub2sub2
AT alexandrasilchenko modulationofdoxorubicinintracellularaccumulationandanticanceractivitybytriterpeneglycosidecucumariosideasub2sub2
AT sergeyavilov modulationofdoxorubicinintracellularaccumulationandanticanceractivitybytriterpeneglycosidecucumariosideasub2sub2
AT dmitryaminin modulationofdoxorubicinintracellularaccumulationandanticanceractivitybytriterpeneglycosidecucumariosideasub2sub2