Suppression of multidrug resistance by migrastatin

Yasushi Takemoto; Etsu Tashiro; Masaya Imoto

doi:10.1038/ja.2006.62

Suppression of multidrug resistance by migrastatin

Yasushi Takemoto, Etsu Tashiro, Masaya Imoto

Department of Biosciences and Informatics

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

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.

Original language	English
Pages (from-to)	435-438
Number of pages	4
Journal	Journal of Antibiotics
Volume	59
Issue number	7
DOIs	https://doi.org/10.1038/ja.2006.62
Publication status	Published - 2006 Jul

Keywords

Anticancer drugs
Migrastatin
Multi drug resistance
P-glycoprotein

ASJC Scopus subject areas

Pharmacology
Drug Discovery

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10.1038/ja.2006.62

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title = "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.",

keywords = "Anticancer drugs, Migrastatin, Multi drug resistance, P-glycoprotein",

author = "Yasushi Takemoto and Etsu Tashiro and Masaya Imoto",

note = "Funding Information: Acknowledgments This study was supported by the project on “Molecules, Supra Molecules and Suprs-Structured Materials” from the Ministry of Education, Culture, Sports, Science and Technology, Japan.",

year = "2006",

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AU - Takemoto, Yasushi

AU - Tashiro, Etsu

AU - Imoto, Masaya

N1 - Funding Information: Acknowledgments This study was supported by the project on “Molecules, Supra Molecules and Suprs-Structured Materials” from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

PY - 2006/7

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N2 - 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.

AB - 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.

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KW - Migrastatin

KW - Multi drug resistance

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