Early apoptotic features of K562 cell death induced by 5-aminolaevulinic acid-based photodynamic therapy.
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.
Kuzelová
K
K
Department of Cellular Biochemistry, Institute of Haematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague 2, Czech Republic. kuzel@uhkt.cz
Grebenová
D
D
Pluskalová
M
M
Marinov
I
I
Hrkal
Z
Z
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020287:In Situ Nick-End Labeling; D020014:K562 Cells; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid