Abstract
The mechanism of cancer cell death induced by KP018, an ethanol extract of the Thai plant Ellipeiopsis cherrevensis, was examined in paclitaxel-resistant HepG2 (PR-HepG2) and colon-26 cells using flow cytometry. In PR-HepG2 cells, KP018 induced necrosis in a concentration-dependent manner. Necrosis of PR-HepG2 cells induced by KP018 as well as by hydrogen peroxide was suppressed by co-treatment of the cells with N-acetylcysteine. KP018 decreased the viability of colon-26 cells with an IC50 value of 15.1 µg/mL, which was estimated by XTT assay. As observed in PR-HepG2 cells, KP018 induced necrosis and the necrosis was suppressed by N-acetylcysteine in colon-26 cells. In addition, using colon-26 solid tumor-bearing mice, KP018 was found to suppress tumor growth without apparent toxicities under in vivo conditions. These results indicate that KP018 induces necrosis rather than apoptosis in these cancer cells, and reactive oxygen species such as hydrogen peroxide would be involved in KP018-induced necrosis. KP018 may be a useful source to search for a new anticancer drug that can be used for the chemotherapy of multidrug-resistant tumors.
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