Early apoptotic features of K562 cell death induced by 5-aminolaevulinic acid-based photodynamic therapy

J Photochem Photobiol B. 2004 Jan 23;73(1-2):67-78. doi: 10.1016/j.jphotobiol.2003.07.007.

Abstract

5-Aminolaevulinic acid-based photodynamic therapy (ALA-PDT) is used to eliminate cancerous cells through photoactivation of endogenously formed protoporphyrin IX (PPIX) following the administration of PPIX precursor, 5-aminolaevulinic acid (ALA). We report on the kinetics of PPIX accumulation and the mechanism of cytotoxic effects of ALA-PDT studied in the chronic myelogenous leukaemia derived cell line K562. The PPIX distribution and, consequently, cytotoxic effects were found to be heterogenous. A subpopulation of K562 cells accumulating PPIX to a lesser extent exhibits only transient cell cycle arrest. A fraction of cells, probably those with higher PPIX accumulation, are irreversibly damaged by ALA-PDT. We detected several signs of an early apoptosis: lowering of Bcl-xL expression, decrease of the mitochondrial and plasma membrane potential, the cytochrome c release into the cytoplasm, and the unmasking of the mitochondrial antigen 7A6. However, late apoptotic events were lacking: neither caspase-3 activation nor DNA fragmentation occurred. Instead, rapidly progressing cell necrosis resulting from plasma membrane damage was observed. We suggest that the high level of the antiapoptotic heat-shock proteins HSP70 and HSP27 found by us in the K562 cells is responsible for the inhibition of the apoptotic process upstream of caspases activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminolevulinic Acid / pharmacology*
  • Apoptosis / drug effects*
  • Cell Division
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Humans
  • In Situ Nick-End Labeling
  • K562 Cells
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology*

Substances

  • Photosensitizing Agents
  • Aminolevulinic Acid