Stress-activated signaling responses leading to apoptosis following photodynamic therapy

Nancy L. Oleinick; Jin He; Liang-yan Xue; Duska Separovic

doi:10.1117/12.308133

19 May 1998 Stress-activated signaling responses leading to apoptosis following photodynamic therapy

Nancy L. Oleinick, Jin He, Liang-yan Xue, Duska Separovic

Proceedings Volume 3247, Optical Methods for Tumor Treatment and Detections: Mechanisms and Techniques in Photodynamic Therapy VII; (1998) https://doi.org/10.1117/12.308133
Event: BiOS '98 International Biomedical Optics Symposium, 1998, San Jose, CA, United States

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.

Citation Download Citation

Nancy L. Oleinick, Jin He, Liang-yan Xue, and Duska Separovic "Stress-activated signaling responses leading to apoptosis following photodynamic therapy", Proc. SPIE 3247, Optical Methods for Tumor Treatment and Detections: Mechanisms and Techniques in Photodynamic Therapy VII, (19 May 1998); https://doi.org/10.1117/12.308133

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