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Overexpression of Bcl-X-L prevents caspase-3-mediated activation of DNA fragmentation factor (DFF) produced by treatment with the photochemotherapeutic agent BPD-MA
Author(s): Granville DJ, Jiang HJ, An MT, Levy JG, McManus BM, Hunt DWC
Source: FEBS LETTERS    Volume: 422    Issue: 2    Pages: 151-154    Published: JAN 30 1998  
Times Cited: 44     References: 24     
Abstract: Photodynamic therapy (PDT) is a clinically effective cancer treatment. For human promyelocytic leukemia HL-60 cells, cleavage of pro-caspase-3 (CPP32/Yama/apopain) into its proteolytically active subunits rapidly follows the photodynamic treatment of these cells with cytotoxic levels of the photosensitizer benzoporphyrin derivative monoacid ring A and visible light. Cleavage of a recently identified cytosolic 45 kDa protein, DNA fragmentation factor (DFF), is required for endonuclease activation leading to DIVA fragmentation. In the present study, DFF was rapidly processed following PDT. Overexpression of the anti-apoptotic Bcl-X-L gene in HL-60 cells prevented PDT-induced caspase activation, DFF cleavage and DIVA fragmentation. These results demonstrate for the first time an example of chemotherapeutic drug-induced activation of DFF and its regulation by Bcl-X-L. (C) 1998 Federation of European Biochemical Societies.
Document Type: Article
Language: English
Reprint Address: Granville, DJ (reprint author), QLT PhotoTherapeut Inc, 520 W 6th Ave, Vancouver, BC V5Z 4H5 Canada
Addresses:
1. QLT PhotoTherapeut Inc, Vancouver, BC V5Z 4H5 Canada
2. Univ British Columbia, St Pauls Hosp, Dept Pathol & Lab Med, Cardiovasc Res Lab, Vancouver, BC V6Z 1Y6 Canada
3. Univ British Columbia, Fac Sci, Dept Microbiol & Immunol, Vancouver, BC V6T 1W5 Canada
Publisher: ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Subject Category: Biochemistry & Molecular Biology; Biophysics; Cell Biology
IDS Number: YW343
ISSN: 0014-5793
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