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

World J Gastroenterol. 2007 Feb 7;13(5):692-8. doi: 10.3748/wjg.v13.i5.692.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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