Abstract
Photodynamic therapy (PDT), utilizing a photosensitizer and visible light, causes localized oxidative damage. With the mitochondrial photosensitizer Pc 4, PDT induces apoptosis, yet its molecular targets are not known. Here, the anti-apoptotic protein Bcl-2 is shown to be highly sensitive to PDT, as judged on Western blots by the disappearance of anti-Bcl-2-reactive material from the position of the native 26 kDa protein. The loss of Bcl-2 was PDT dose dependent and was observed for both endogenous and overexpressed Bcl-2 in several cell lines, immediately after PDT, and with chilled cells. It was accompanied by a trace of a 23-kDa cleavage product as well as high-molecular weight products that may result from photochemical crosslinking. PDT-induced Bcl-2 loss occurred in MCF-7 cells that do not express caspase-3 or in the presence of protease inhibitors, but was prevented, along with the induction of apoptosis, by the singlet oxygen scavenger L-histidine. Loss of FLAG-Bcl-2 was observed with both anti-FLAG and anti-Bcl-2 antibodies, indicating loss of native protein rather than simple BCL-2-epitope destruction. Photochemical damage was not observed in Bcl-xL, Bax, Bad, the voltage-dependent anion channel, or the adenine nucleotide translocator. Therefore, Bcl-2 is one target of PDT with Pc 4, and PDT damage to Bcl-2 contributes to its efficient induction of apoptosis.
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Acknowledgements
The authors thank Drs Christopher J Froelich, David A Boothman, John J Pink and Sarah M Planchon for providing some of the cell lines used in this study. This research was supported by U.S. Public Health Service Grants P01 CA48735, R01 CA83917, and P30 CA43703 from the National Cancer Institute, DHHS.
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Xue, Ly., Chiu, Sm. & Oleinick, N. Photochemical destruction of the Bcl-2 oncoprotein during photodynamic therapy with the phthalocyanine photosensitizer Pc 4. Oncogene 20, 3420–3427 (2001). https://doi.org/10.1038/sj.onc.1204441
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DOI: https://doi.org/10.1038/sj.onc.1204441
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