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Molecular mechanisms of denbinobin-induced anti-tumorigenesis effect in colon cancer cells

World Journal of Gastroenterology 2005年第20期11卷 3040-3045页

作者： Kuo-Ching Yang Yih-Huei Uen Fat-Moon Suk Yu-Chih Liang Ying-Jan Wang Yuan-Soon Ho I-Hsuan Li Shyr-Yi Lin Department of Internal Medicine Shin Kong Wu Ho-Su Memorial Hospital Taipei Taiwan Department of Internal Medicine Taipei Medical University Taipei Taiwan China Department of Surgery Chi-Mei Foundational Medical Center Yung-Kane City Tainan Taiwan China Department of Internal Medicine Taipei Medical University Hospital Taipei Taiwan China School of Medical Technology Taipei Medical University Taipei Taiwan China Department of Environmental and Occupational Health National Cheng Kung University Medical College TainanTaiwan China Department of Internal Medicine School of Medicine Taipei Medical University Taipei Taiwan China Department of Internal Medicine School of Medicine and Department of Internal Medicine Taipei Medical University Hospital Taipei Medical University Taipei Taiwan China

AIM: To explore both the in vitro and in vivo effects of denbinobin against colon cancer cells and clarify its underlying signal pathways. METHODS: We used COLO 205 cancer cell lines and nude mice xenograft model to study the in vitro and in vivo anti-cancer effects of denbinobin. RESULTS: denbinobin at concentration of 10-20 μmol/L dose-dependently suppressed COLO 205 cell proliferation by MTT test. Flow cytometry analysis and DNA fragmentation assay revealed that 10-20 μmol/L denbinobin treatment induced COLO 205 cells apoptosis. Western blot analysis showed that caspases 3,8,9 and Bid protein were activated by denbinobin treatment to COLO 205 cells accompanied with cytochrome c and apoptosis-inducing factor (AIF) translocation. Pretreatment of MEK 1 inhibitor (U10126), but not p38 inhibitor (SB203580) and JNK inhibitor (SP600125), reversed denbinobin-induced caspase 8, 9 and Bid activation in COLO 205 cells suggesting that extracellular signal-regulated kinase were involved in the denbinobin-induced apoptosis in COLO 205 cells. Significant regression of tumor up to 68% was further demonstrated in vivo by treating nude mice bearing COLO 205 tumor xenografts with denbinobin 50 mg/kg intraperitoneally. CONCLUSION: Our findings suggest that denbinobin could inhibit colon cancer growth both in vitro and in vivo. Activation of extrinsic and intrinsic apoptotic pathways and AIF were involved in the denbinobin-induced COLO 205 cell apoptosis.

关键词： denbinobin Colon cancer Nude mice Apoptosis ERK pathway

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