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Euphorbiasteroid Reverses P-glycoprotein-mediated Multi-Drug Resistance in Human Sarcoma Cell Line MES-SA/Dx5

Euphorbiasteroid Reverses P-glycoprotein-mediated Multi-Drug Resistance in Human Sarcoma Cell Line MES-SA/Dx5

Jung Sook Choi, Nam Sook Kang, Yong Ki Min, Seong Hwan Kim

Phytother Res. 2010 Jul;24(7):1042-6.

PMID: 19960428

Abstract:

In this study, we evaluated whether euphorbiasteroid isolated from Euphorbia lathyris has the potential to reverse P-glycoprotein (P-gp)-mediated multi-drug resistance (MDR) by using the drug-sensitive human sarcoma cell line MES-SA and its MDR counterpart MES-SA/Dx5. Interestingly, even at low concentrations of euphorbiasteroid (1-3 microM), it efficiently restored the toxicities of anticancer drugs including vinblastine, taxol and doxorubicin in MES-SA/Dx5 cells. Additionally, the computational Bayesian model for predicting potential P-gp substrates or inhibitors revealed that euphorbiasteroid showed 97% probability for substrate likeness having similar molecular features with 50 P-gp substrates. Consistent with this result, the substrate likeness of euphorbiasteroid was also experimentally confirmed by P-gp ATPase activity assay. In conclusion, our finding suggested that euphorbiasteroid could be a transport substrate for P-gp that can effectively inhibit P-gp-mediated drug transport and reverse resistance to anticancer drugs in MES-SA/Dx5 cells.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP28649594	Euphorbiasteroid		28649-59-4	Price

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