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Proceedings Paper

Stress-activated signaling responses leading to apoptosis following photodynamic therapy
Author(s): Nancy L. Oleinick; Jin He; Liang-yan Xue; Duska Separovic
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Paper Abstract

Photodynamic treatment with the phthalocyanine Pc 4, a mitochondrially localizing photosensitizer, is an efficient inducer of cell death by apoptosis, a cell suicide pathway that can be triggered by physiological stimuli as well as by various types of cellular damage. Upon exposure of the dye- loaded cells to red light, several stress signalling pathways are rapidly activated. In murine L5178Y-R lymphoblasts, caspase activation and other hallmarks of the final phase of apoptosis are observed within a few minutes post-PDT. In Chinese hamster CHO-K1 cells, the first signs of apoptosis are not observed for 1 - 2 hours. The possible involvement of three parallel mitogen-activated protein kinase (MAPK) signalling pathways has been investigated. The extracellular- regulated kinases (ERK-1 and ERK-2), that are thought to promote cell growth, are not appreciably altered by PDT. However, PDT causes marked activation of the stress-activated protein kinase (SAPK) cascade in both cell types and of the p38/HOG-type kinase in CHO cells. Both of these latter pathways have been demonstrated to be associated with apoptosis. A specific inhibitor of the ERK pathway did not alter PDT-induced apoptosis; however, an inhibitor of the p38 pathway partially blocked PDT-induced apoptosis. Blockage of the SAPK pathway is being pursued by a genetic approach. It appears that the SAPK and p38 pathways may participate in signaling apoptosis in response to PDT with Pc 4.

Paper Details

Date Published: 19 May 1998
PDF: 7 pages
Proc. SPIE 3247, Optical Methods for Tumor Treatment and Detections: Mechanisms and Techniques in Photodynamic Therapy VII, (19 May 1998); doi: 10.1117/12.308133
Show Author Affiliations
Nancy L. Oleinick, Case Western Reserve Univ. School of Medicine (United States)
Jin He, Case Western Reserve Univ. School of Medicine (United States)
Liang-yan Xue, Case Western Reserve Univ. School of Medicine (United States)
Duska Separovic, Case Western Reserve Univ. School of Medicine (United States)


Published in SPIE Proceedings Vol. 3247:
Optical Methods for Tumor Treatment and Detections: Mechanisms and Techniques in Photodynamic Therapy VII
Thomas J. Dougherty, Editor(s)

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