| Summary: | 碩士 === 中華醫事科技大學 === 生物科技系暨生物醫學研究所 === 102 === Colorectal cancer is one of the most commonly diagnosed tumors worldwide and is known to be resistant to conventional chemotherapy. Osthole, a natural coumarin derivative, has been shown to have antitumor activity mediated by the modulation of oxidative stress. Nitric oxide (NO) is important mediator of the expression of many transcription factors and signaling cascades that affect tumor responses to therapy. However, the effects of osthole and NO on cell growth of colorectal cancer are not well understood. The aim of this study was to investigate the effects and mechanisms of osthole and NO on proliferation in colorectal cancer cells. We found that exposure of two human colorectal adenocarcinoma cell lines (HT-29 and SW-480) to osthole and NO donors S-nitroso-N-acetylpenicillamine (SNP) and sodium nitroprusside (SNAP) significantly inhibited the cell growth in concentration- and time-dependent manners. Osthole and NO donors had no significant effect on cytotoxicity as compared with control. Additionally, treatments of osthole and NO donors enhanced NO generation and iNOS (but not eNOS) protein synthesis. Furthermore, osthole and NO donors could suppress activation of the JAK2 and ERK/p38 MAPK pathway in these cells. The JAK2 inhibitor AG490, the ERK inhibitor PD98059 and the p38 MAPK inhibitor SB203580 may have the ability to decrease cellular proliferation. The results obtained in this study suggest the new mechanistic evidence that osthole and exogenous NO donors attenuate the cell growth by inhibiting the JAK2 and ERK/p38 MAPK activation and promoting the iNOS/NO pathway in HT-29 and SW-480 cells.
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