title: Protection by Bcl-2 against apoptotic but not autophagic cell death after photodynamic therapy.
abstract: Photodynamic therapy (PDT) induces apoptosis in many cell types. Recent reports identified autophagy as an alternative cell-death process following PDT. Here we investigated the occurrence of autophagy after PDT with the photosensitizer Pc 4 in human cancer cells that are deficient in the pro-apoptotic factor Bax (human prostate cancer DU145) or the apoptosis mediator caspase-3 (human breast cancer MCF-7v) and in apoptosis-competent cells (MCF-7c3 stably overexpressing human pro-caspase-3 and Chinese hamster ovary CHO 5A100). Further, each cell line was also studied with and without stably overexpressed Bcl-2. By electron microscopy and immunoblot analysis, autophagy was observed in all cells studied, whether or not they were capable of typical apoptosis or overexpressed Bcl-2. Bcl-2 overexpression protected against PDT-induced apoptosis and loss of clonogenicity in apoptosis-competent cells (MCF-7c3 and CHO); however, it did not protect against the development of autophagy or against loss of clonogenicity in apoptosis-deficient cells (MCF-7v and DU145). The results show that autophagy may be the dominant cell death pathway following PDT in cells that are incapable of undergoing normal apoptosis. In such cells, Bcl-2 does not protect against autophagic death.
authors.affiliation: Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4942, USA.
authors.forename: Liang-yan
authors.initials: LY
authors.lastname: Xue
authors.forename: Song-mao
authors.initials: SM
authors.lastname: Chiu
authors.forename: Kashif
authors.initials: K
authors.lastname: Azizuddin
authors.forename: Sheeba
authors.initials: S
authors.lastname: Joseph
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Oleinick
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D010588:Phagosomes / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
chemical_list: D017319:Photosensitizing Agents; D019253:Proto-Oncogene Proteins c-bcl-2