Suppression of multidrug resistance by migrastatin.

Abstract

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.

• Authors: Yasushi Takemoto, Etsu Tashiro, Masaya Imoto
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 59 Issue 7 Pg. 435-8 (Jul 2006) ISSN: 0021-8820 [Print] England
• PMID: 17025021 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Lactones
• Macrolides
• Piperidones
• migrastatin
• Vincristine
• Vinblastine
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm (drug effects)
• Humans
• Lactones (pharmacology)
• Macrolides (pharmacology)
• Mice
• Paclitaxel (pharmacology)
• Piperidones (pharmacology)
• Vinblastine (pharmacology)
• Vincristine (pharmacology)