Colorectal Cancer
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 7, 2007; 13(5): 692-698
Published online Feb 7, 2007. doi: 10.3748/wjg.v13.i5.692
Early apoptosis and cell death induced by ATX-S10Na (II)-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells
Makoto Mitsunaga, Akihito Tsubota, Kohichi Nariai, Yoshihisa Namiki, Makoto Sumi, Tetsuya Yoshikawa, Kiyotaka Fujise
Makoto Mitsunaga, Akihito Tsubota, Kohichi Nariai, Yoshihisa Namiki, Makoto Sumi, Tetsuya Yoshikawa, Kiyotaka Fujise, Institute of Clinical Medicine and Research, Jikei University School of Medicine, Kashiwa, Chiba, Japan
Makoto Mitsunaga, Kiyotaka Fujise, Division of Gastro-enterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
Author contributions: All authors contributed equally to the work.
Supported by a grant from the Jikei University School of Medicine
Correspondence to: Makoto Mitsunaga, MD, Institute of Clinical Medicine and Research, Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba 277-8567, Japan. mit@jikei.ac.jp
Telephone: +81-4-71641111 Fax: +81-4-71668638
Received: October 20, 2006
Revised: December 1, 2006
Accepted: December 20, 2006
Published online: February 7, 2007
Abstract

AIM: To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na (II).

METHODS: HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin V assays, transmission electron microscopy assays, caspase assays and western blotting.

RESULTS: Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti-apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-xL, were decreased in Bax- and p53-independent manner.

CONCLUSION: Our results indicate that early apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizing photosensitizer ATX-S10Na (II) are mediated by p53-Bax network and low levels of Bcl-2 and Bcl-xL proteins. Our results might help in formulating new therapeutic approaches in photodynamic therapy.

Keywords: Photodynamic therapy, ATX-S10Na (II), Apoptosis, Bax, p53