Reactive oxygen species-mediated induction of apoptosis by a plant alkaloid 6-methoxydihydrosanguinarine in HepG2 cells.
We have found in the previous study that 6-methoxydihydrosanguinarine (6ME), a benzophenanthridine alkaloid isolated from Hylomecon species, may have potential as a chemotherapeutic agent. However, the mechanisms of 6ME-induced cell death have not been investigated. The purpose of the present study was to determine the apoptosis-inducing potential of 6ME in human hepatocarcinoma HepG2 cells and the role of reactive oxygen species in 6ME-induced apoptosis. It can be concluded from the results that 6ME inhibits the growth of HepG2 cells in a concentration- and time-dependent manner (IC50=3.8+/-0.2 microM following 6 h incubation). Treatment of HepG2 cells with 6ME resulted in the release of mitochondrial cytochrome c followed by the activation of caspase proteases, and subsequent proteolytic cleavage of poly(ADP-ribose) polymerase. 6ME increased the expression of p53 and bax and decreased the expression of bcl-2. The cytotoxic effect of 6ME is mediated by the time-dependent generation of reactive oxygen species. Our results also show that preincubation of HepG2 cells with vitamin C decreased the expression of p53 and bax and inhibited the release of cytochrome c, activation of downstream caspase and the cleavage of poly(ADP-ribose) polymerase, thus inhibiting the apoptosis inducing effect of 6ME.
Yin
Hu-Quan
HQ
College of Pharmacy, Seoul National University, San 56-1 Sillim-dong, Gwanak-gu, Seoul 151-742, Republic of Korea.
Kim
Young-Ho
YH
Moon
Chang-Kiu
CK
Lee
Byung-Hoon
BH
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053119:Benzophenanthridines; D045744:Cell Line, Tumor; D006801:Humans; D007546:Isoquinolines; D010617:Phenanthridines / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*
C438021:6-methoxydihydrosanguinarine; D000470:Alkaloids; D053119:Benzophenanthridines; D007546:Isoquinolines; D010617:Phenanthridines; D010936:Plant Extracts; D017382:Reactive Oxygen Species