Suppression of multidrug resistance by migrastatin.
Migrastatin (MGS) is a Streptomyces metabolite that inhibits cancer cell migration. In this study, we found that MGS also enhanced the cytotoxicity of vinblastine, vincristine, and taxol in P-glycoprotein-overexpressing VJ-300 cells and P388/VCR cells. Furthermore, MGS increased the intracellular concentration of labeled vinblastine, vincristine, and taxol in both VJ-300 cells and P388/VCR cells. P-glycoprotein was photolabeled with [3H]azidopine, but this photolabeling was significantly inhibited in the presence of MGS. These results indicated that MGS directly interacts with and inhibits P-glycoprotein, thereby sensitizing drug-resistant cells to anticancer drugs.
Takemoto
Yasushi
Y
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
Tashiro
Etsu
E
Imoto
Masaya
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D018942:Macrolides / Q000494:pharmacology*; D051379:Mice; D017239:Paclitaxel / Q000494:pharmacology; D010881:Piperidones / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D007783:Lactones; D018942:Macrolides; D010881:Piperidones; C418199:migrastatin; D014750:Vincristine; D014747:Vinblastine; D017239:Paclitaxel