Nitric oxide activated by p38 and NF-kappaB facilitates apoptosis and cell cycle arrest under oxidative stress in evodiamine-treated human melanoma A375-S2 cells |
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| Authors: | Yang Jia Wu Li-Jun Tashiro Shin-Ichi Onodera Satoshi Ikejima Takashi |
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| Affiliation: | a China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang, PR, Chinab Department of Phytochemistry, Shenyang Pharmaceutical University, Shenyang, PR, Chinac Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo, Japan |
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| Abstract: | Nitric oxide (NO) has been identified as a fundamental molecule that interplays with reactive oxygen species (ROS) in determining cell fate. As a previous study indicated that ROS was stimulated in evodiamine-induced human melanoma A375-S2 cell apoptosis, the goal of this study was to investigate the role of NO in the cells. In this study, it was found that evodiamine has a strong inductive effect on NO production synthesized by inducible NOS (iNOS) enzyme in a positive-feedback manner. The generated NO was further showed to induce apoptosis and cell cycle arrest and linked to the activation of p53 and p21. After interruption of p38 and nuclear factor-κB (NF-κB) by pre-treatment with SB203580 and PDTC, iNOS expression, NO synthesis and cell damage were all significantly blocked. It was concluded that p38 and NF-κB were critical to the NO producing system, which contributed greatly to the apoptosis and cell cycle arrest in evodiamine-incubated cells. |
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| Keywords: | Evodiamine nitric oxide (NO) inducible NOS (iNOS) apoptosis cell cycle arrest p38 MAPK nuclear factor-κB (NF-κB) |
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