Euphorbiasteroid reverses P-glycoprotein-mediated multi-drug resistance in human sarcoma cell line MES-SA/Dx5.

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.

• Authors: Jung Sook Choi, Nam Sook Kang, Yong Ki Min, Seong Hwan Kim
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 24 Issue 7 Pg. 1042-6 (Jul 2010) ISSN: 1099-1573 [Electronic] England
• PMID: 19960428 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents, Phytogenic
• Diterpenes
• Phenylacetates
• euphorbiasteroid

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
• Bayes Theorem
• Cell Line, Tumor
• Diterpenes (isolation & purification, pharmacology)
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Euphorbia (chemistry)
• Female
• Humans
• Models, Chemical
• Phenylacetates (isolation & purification, pharmacology)
• Sarcoma (metabolism)
• Uterine Neoplasms (metabolism)