Colorectalcancer
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 28, 2007; 13(20): 2811-2818
Published online May 28, 2007. doi: 10.3748/wjg.v13.i20.2811
Mechanisms involved in Korean mistletoe lectin-induced apoptosis of cancer cells
Lee-Yong Khil, Wi Kim, Suyun Lyu, Won Bong Park, Ji-Won Yoon, Hee-Sook Jun
Lee-Yong Khil, Wi Kim, Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Canada
Suyun Lyu, Immune Modulation Group, Boots Science Building, School of Pharmacy, University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom
Won Bong Park, College of Natural Science, Seoul Women’s University, Seoul 139-774, Korea
Ji-Won Yoon, Hee-Sook Jun, Department of Pathology, Chicago Medical School, North Chicago, IL, 60064, United States Sadly, Dr. Ji-Won Yoon passed away on April 6, 2006
Author contributions: All authors contributed equally to the work.
Supported by the International Innovative Biotechnology Institute
Correspondence to: Hee-Sook Jun, Department of Pathology, Chicago Medical School, North Chicago, IL, 60064, United States. hee-sook.jeon@rosalindfranklin.edu
Telephone: +1-847-5788341 Fax: +1-847-5783432
Received: December 16, 2006
Revised: March 3, 2007
Accepted: March 19, 2007
Published online: May 28, 2007
Abstract

AIM: To investigate the anti-cancer mechanisms of Korean mistletoe lectin (Viscum album coloratum agglutinin, VCA) using a human colon cancer cell line (COLO).

METHODS: Cytotoxic effects of VCA on COLO cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro and tumor-killing effects in vivo. To study the mechanisms involved, the expression of various pro-caspases, anti-apoptotic proteins, and death receptors was determined by western blot. To determine which death receptor is involved in VCA-induced apoptosis of COLO cells, cytotoxicity was examined by MTT assay after treatment with agonists or antagonists of death receptors.

RESULTS: VCA killed COLO cells in a time- and dose-dependent manner and induced complete regression of tumors in nude mice transplanted with COLO cells. Treatment of COLO cells with VCA activated caspase-2, -3, -8, and -9 and decreased expression of anti-apoptotic molecules including receptor interacting protein, nuclear factor-κB, X-linked inhibitor of apoptosis protein, and Akt/protein kinase B. We then examined the involvement of death receptors in VCA-induced apoptosis. Only tumor necrosis factor receptor 1, among the death receptors examined, was involved in apoptosis of COLO cells, evidenced by inhibition of VCA-induced apoptosis and decreased activation of caspases, particularly caspase-8, by tumor necrosis factor receptor 1 antagonizing antibody.

CONCLUSION: VCA-induced apoptotic COLO cell death is due to the activation of caspases and inhibition of anti-apoptotic proteins, in part through the tumor necrosis factor receptor 1 signaling pathway.

Keywords: Viscum album coloratum; Lectin; Apoptosis; Tumor necrosis factor receptor-1; Caspase; Colon cancer