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Proceedings Paper

Signaling from lysosomes to mitochondria sensitizes cancer cells to photodynamic treatment
Author(s): Hsin-I Hung; Geraldine Quiogue; John J. Lemasters; Anna-Liisa Nieminen
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Paper Abstract

Previously, we showed that photosensitizers that localize to lysosomes are more effective in killing cancer cells than ones directed to mitochondria after photodynamic treatment (PDT). The photosensitizer, phthalocyanine 4 (Pc 4), localizes primarily to mitochondrial membranes in cancer cells, resulting in mitochondria-mediated cell death. However, analogues of Pc 4 (e.g., Pc 181) that primarily target lysosomes still produce mitochondria-mediated cell death, although the time course is slower compared to Pc 4-PDT. In A431 epidermoid carcinoma cells, these new analogues preferentially localized in lysosomes were highly efficient in inducing apoptotic cell death. To assess further how lysosomes contribute to PDT, we monitored cell killing of A431 cells after Pc 4-PDT in the presence and absence of bafilomycin, an inhibitor of the acidic vacuolar proton pump that collapses the pH gradient of the lysosomal/endosomal compartment. Bafilomycin by itself was not toxic but greatly enhanced Pc 4-PDT-induced mitochondrial depolarization and cell killing. Both depolarization and cell killing were substantially prevented by iron chelators. The fact that Pc 4-PDT plus bafilomycin treatment did not induce lysosomal membrane damage prior to mitochondrial depolarization suggests that bafilomycin instead induced release of redox active iron from lysosomes into the cytosol that further translocated into mitochondria, where iron-mediated free radical formation occurred. In conclusion, agents that disturb lysosomal function could potentially be used as adjuvants with mitochondrion-targeted photosensitizers to enhance phototoxicity.

Paper Details

Date Published: 17 February 2011
PDF: 6 pages
Proc. SPIE 7886, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX, 78860C (17 February 2011); doi: 10.1117/12.878306
Show Author Affiliations
Hsin-I Hung, Medical Univ. of South Carolina (United States)
Geraldine Quiogue, Medical Univ. of South Carolina (United States)
John J. Lemasters, Medical Univ. of South Carolina (United States)
Anna-Liisa Nieminen, Medical Univ. of South Carolina (United States)

Published in SPIE Proceedings Vol. 7886:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX
David H. Kessel; Tayyaba Hasan, Editor(s)

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