Early apoptosis and cell death induced by ATX-S10Na (II)-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells.

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-x(L), 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-x(L) proteins. Our results might help in formulating new therapeutic approaches in photodynamic therapy.

• Authors: Makoto Mitsunaga, Akihito Tsubota, Kohichi Nariai, Yoshihisa Namiki, Makoto Sumi, Tetsuya Yoshikawa, Kiyotaka Fujise
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 13 Issue 5 Pg. 692-8 (Feb 07 2007) ISSN: 1007-9327 [Print] United States
• PMID: 17278191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATX S10Na(II)
• Photosensitizing Agents
• Porphyrins
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein

Topics

• Apoptosis (drug effects, physiology)
• Colonic Neoplasms (pathology)
• HCT116 Cells
• Humans
• Photochemotherapy
• Photosensitizing Agents (pharmacology)
• Porphyrins (pharmacology)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• bcl-2-Associated X Protein (genetics, metabolism)