title: 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: Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology, Daejeon, Korea.
authors: Jung Sook
authors: JS
authors: Choi
authors: Nam Sook
authors: NS
authors: Kang
authors: Yong Ki
authors: YK
authors: Min
authors: Seong Hwan
authors: SH
authors: Kim
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D001499:Bayes Theorem; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D028481:Euphorbia / Q000737:chemistry*; D005260:Female; D006801:Humans; D008956:Models, Chemical; D010648:Phenylacetates / Q000302:isolation & purification / Q000494:pharmacology*; D012509:Sarcoma / Q000378:metabolism; D014594:Uterine Neoplasms / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D010648:Phenylacetates; C551893:euphorbiasteroid