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Proceedings Paper

Autophagy in response to photodynamic therapy: cell survival vs. cell death
Author(s): Nancy L. Oleinick; Liang-yan Xue; Song-mao Chiu; Sheeba Joseph
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Paper Abstract

Autophagy (or more properly, macroautophagy) is a pathway whereby damaged organelles or other cell components are encased in a double membrane, the autophagosome, which fuses with lysosomes for digestion by lysosomal hydrolases. This process can promote cell survival by removing damaged organelles, but when damage is extensive, it can also be a mechanism of cell death. Similar to the Kessel and Agostinis laboratories, we have reported the vigorous induction of autophagy by PDT; this was found in human breast cancer MCF-7 cells whether or not they were able to efficiently induce apoptosis. One way to evaluate the role of autophagy in PDT-treated cells is to silence one of the essential genes in the pathway. Kessel and Reiners silenced the Atg7 gene of murine leukemia L1210 cells using inhibitory RNA and found sensitization to PDT-induced cell death at a low dose of PDT, implying that autophagy is protective when PDT damage is modest. We have examined the role of autophagy in an epithelium-derived cancer cell by comparing parental and Atg7-silenced MCF-7 cells to varying doses of PDT with the phthalocyanine photosensitizer Pc 4. In contrast to L1210 cells, autophagy-deficient MCF-7 cells were more resistant to the lethal effects of PDT, as judged by clonogenic assays. A possible explanation for the difference in outcome for L1210 vs. MCF-7 cells is the greatly reduced ability of the latter to undergo apoptosis, a deficiency that may convert autophagy into a cell-death process even at low PDT doses. Experiments to investigate the mechanism(s) responsible are in process.

Paper Details

Date Published: 18 February 2009
PDF: 9 pages
Proc. SPIE 7164, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XVIII, 716403 (18 February 2009); doi: 10.1117/12.810933
Show Author Affiliations
Nancy L. Oleinick, Case Western Reserve Univ. (United States)
Liang-yan Xue, Case Western Reserve Univ. (United States)
Song-mao Chiu, Case Western Reserve Univ. (United States)
Sheeba Joseph, Case Western Reserve Univ. (United States)


Published in SPIE Proceedings Vol. 7164:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XVIII
David H. Kessel, Editor(s)

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