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Trisindoline synthesis and anticancer activity |
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| Authors: | Yoo Miyoun Choi Sang-Un Choi Ki Young Yon Gyu Hwan Chae Jong-Chan Kim Dockyu Zylstra Gerben J Kim Eungbin |
| Affiliation: | a Department of Biology, Yonsei University, 134 Shinchon, Seoul 120-749, Republic of Korea b Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea c Polar BioCenter, Korea Polar Research Institute, KORDI, Incheon 406-840, Republic of Korea d Biotechnology Center for Agriculture and the Environment, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ 08901-8520, USA |
| Abstract: | Expression of a Rhodococcus-derived oxygenase gene in Escherichia coli yielded indigo metabolites with cytotoxic activity against cancer cells. Bioactivity-guided fractionation of these indigo metabolites led to the isolation of trisindoline as the agent responsible for the observed in vitro cytotoxic activity against cancer cells. While the cytotoxicity of etoposide, a common anticancer drug, was dramatically decreased in multidrug-resistant (MDR) cancer cells compared with treatment of parental cells, trisindoline was found to have similar cytotoxicity effects on both parental and MDR cell lines. In addition, the cytotoxic effects of trisindoline were resistant to P-glycoprotein overexpression, one of the most common mechanisms of drug resistance in cancer cells, supporting its use to kill MDR cancer cells. |
| Keywords: | Rhodococcus Oxygenase Trisindoline MDR cancer cells Anticancer activity |
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