Abstract
Caspases have been shown to play a crucial role in apoptosis induced by various deleterious and physiologic stimuli. In this study, we show for the first time that photodynamic therapy (PDT), using benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) as the photosensitizer, induces the complete cleavage and subsequent activation of caspase-3 (CPP32/Yama/Apopain) but not caspase-1 (ICE) in human promyelocytic leukemia HL-60 cells. Poly(ADP-ribose) polymerase (PARP) and the catalytic subunit of DNA dependent protein kinase (DNA PKCS) were cleaved within 60 min of light activation of BPD-MA. The general caspase inhibitor Z-Asp-2,6 dichlorobenzoyloxymethylketone (Z-Asp-DCB) blocked PARP cleavage while the serine protease inhibitors 3,4-dichloroisocoumarin (DCI) and N-tosyl-lysyl chloromethyl ketone (TLCK) blocked the cleavage of caspase-3 suggesting that they act upstream of caspase-3 activation. All three inhibitors were able to block DNA fragmentation that was induced by treatment with BPD-MA followed by light application. These studies demonstrate that protease activity, particularly that of caspase-3, is triggered in HL-60 cells treated with lethal levels of BPD-MA and visible light.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Granville, D., Levy, J. & Hunt, D. Photodynamic therapy induces caspase-3 activation in HL-60 cells. Cell Death Differ 4, 623–628 (1997). https://doi.org/10.1038/sj.cdd.4400286
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.cdd.4400286
Keywords
This article is cited by
-
Involvement of retinoblastoma (Rb) and E2F transcription factors during photodynamic therapy of human epidermoid carcinoma cells A431
Oncogene (1999)
-
Different apoptotic pathways are induced from various intracellular sites by tetraphenylporphyrins and light
British Journal of Cancer (1999)
-
Bcl-2 overexpression blocks caspase activation and downstream apoptotic events instigated by photodynamic therapy
British Journal of Cancer (1999)
-
A photodynamic pathway to apoptosis and necrosis induced by dimethyl tetrahydroxyhelianthrone and hypericin in leukaemic cells: possible relevance to photodynamic therapy
British Journal of Cancer (1999)