Fw: Up-Regulation of Clusterin during Phthalocyanine 4 Photodynamic Therapy-mediated Apoptosis of Tumor Cells and Ablation of Mouse Skin Tumors1

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Subject: Up-Regulation of Clusterin during Phthalocyanine 4 Photodynamic Therapy-mediated Apoptosis of Tumor Cells and Ablation of Mouse Skin Tumors1

[Cancer Research 60, 5984-5987, November 1, 2000] © 2000 American Association for Cancer Research Advances in Brief Up-Regulation of Clusterin during Phthalocyanine 4 Photodynamic Therapy-mediated Apoptosis of Tumor Cells and Ablation of Mouse Skin Tumors1 Katrin Kalka, Nihal Ahmad, Criswell, Boothman and Hasan Mukhtar2 Departments of Dermatology [K. K., N. A., H. M.] and Radiation Oncology [T. C., D. B., H. M.], Case Western Reserve University, Cleveland, Ohio 44106 ------------ Photodynamic therapy (PDT) using the silicon phthalocyanine photosensitizer Pc 4 is an oxidative stress associated with the induction of apoptosis in many cancer cells in vitro and in vivo. The mechanisms of PDT-induced tumor cell killing leading to apoptosis are incompletely understood. Clusterin, a widely expressed glycoprotein, is induced in tissues regressing as a consequence of oxidative stress-mediated cell death. Treatment of apoptosis-sensitive human epidermoid carcinoma cells (A431) with PDT resulted in significant up-regulation of clusterin with a maximum at 12 h after treatment, whereas clusterin levels in Pc 4-PDT-treated, apoptosis-resistant, radiation-induced fibrosarcoma (RIF-1) cells remained unchanged. The i.v. administration of Pc 4 to mice bearing chemically or UVB radiation-induced skin papillomas, followed by light application, led to increased clusterin protein expression, peaking 24 h after the treatment, when tumor regression was apparently visible. These data, for the first time, demonstrate the involvement of clusterin in PDT-mediated cell death and during tumor regression. This may have relevance in improving the efficacy of PDT using pharmacological inducers of clusterin. http://sageke.sciencemag.org/cgi/content/abstract/canres;60/21/5984?ck=nck & fulltext=silicone & searchid=QID_NOT_SET