Trisindoline synthesis and anticancer activity.
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.
Yoo
Miyoun
M
Department of Biology, Yonsei University, 134 Shinchon, Seoul 120-749, Republic of Korea.
Choi
Sang-Un
SU
Choi
Ki Young
KY
Yon
Gyu Hwan
GH
Chae
Jong-Chan
JC
Kim
Dockyu
D
Zylstra
Gerben J
GJ
Kim
Eungbin
E