Regulation of ERK MAPK in evodiamine-induced A375-S2 cell death |
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Authors: | ZHANG Ying ZHANG Qi-hui WU Li-jun TASHIRO Shin-ichi ONODERA Satoshi IKEJIMA Takashi |
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Affiliation: | 1. China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China;2. Department of Natural Product, Shenyang Pharmaceutical University, Shenyang 110016, China;3. Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo 194-8543, Japan |
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Abstract: | AIM: To compare the cytotoxic effect of evodiamine with chemotherapy drugs on A375-S2 cells, and to examine the relationship between the effects of PKC and ERK on evodiamine-induced cell death. METHODS: MTT assay and Western blot analysis were applied. RESULTS: Compared to actinomycin D, cisplatin and 5-FU, evodiamine showed less cytotoxic effects on A375-S2 cells, but it induced more significant inhibition of proliferation in A375-S2 cells incubated with evodiamine for 24 h, followed by continuous culture in drug-free medium. The activation of PKC induced by 10 μg·L-1 PMA partially blocked evodiamine-induced cell death, which was reversed by PKC and ERK inhibitors. Moreover, evodiamine down-regulated the expressions of ERK and phosphorylated ERK. CONCLUSION: Evodiamine has a strong inhibitory influence on proliferation of A375-S2 cells, even after removal of evodiamine. Evodiamine blocks the protective role of ERK to A375-S2 cells through the downregulation of ERK and phosphorylated ERK expression. |
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Keywords: | Evodiamine Melanoma A375-S cells Mitogen-activated protein kinases |
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