Colorectal Cancer
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2005; 11(20): 3040-3045
Published online May 28, 2005. doi: 10.3748/wjg.v11.i20.3040
Molecular mechanisms of denbinobin-induced anti-tumorigenesis effect in colon cancer cells
Kuo-Ching Yang, Yih-Huei Uen, Fat-Moon Suk, Yu-Chih Liang, Ying-Jan Wang, Yuan-Soon Ho, I-Hsuan Li, Shyr-Yi Lin
Kuo-Ching Yang, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Department of Internal Medicine, Taipei Medical University, Taipei, Taiwan, China
Yih-Huei Uen, Department of Surgery, Chi-Mei Foundational Medical Center, Yung-Kang City, Tainan, Taiwan, China
Fat-Moon Suk, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, China
Yu-Chih Liang, School of Medical Technology, Taipei Medical University, Taipei, Taiwan, China
Ying-Jan Wang, Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan, China
Yuan-Soon Ho, School of Medical Technology, Taipei Medical University, Taipei, Taiwan, China
I-Hsuan Li, Department of Internal Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan, China
Shyr-Yi Lin, Department of Internal Medicine, School of Medicine and Department of Internal Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan, China
Author contributions: All authors contributed equally to the work.
Supported by the Shin Kong Wu Ho-Su Memorial Hospital (SKH-TMU-93-16) and the Chi Mei Medical Center (93CM-TMU-09)
Correspondence to: Dr. Shyr-Yi Lin, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan, China. sylin@tmu.edu.tw
Telephone: +886-2-27361661-3210 Fax: +886-2-27393447
Received: October 26, 2004
Revised: October 28, 2004
Accepted: December 23, 2004
Published online: May 28, 2005
Abstract

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.

Keywords: Denbinobin, Colon cancer, Nude mice, Apoptosis, ERK pathway