Up-regulation of clusterin during phthalocyanine 4 photodynamic therapy-mediated apoptosis of tumor cells and ablation of mouse skin tumors.

Authors: Kalka, K  Ahmad, N  Criswell, T  Boothman, D  Mukhtar, H 
Citation: Kalka K, etal., Cancer Res. 2000 Nov 1;60(21):5984-7.
Pubmed: (View Article at PubMed) PMID:11085517

Photodynamic therapy (PDT) using the silicon phthalocyanine photo-sensitizer 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.


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CRRD Object Information
CRRD ID: 8746700
Created: 2014-08-14
Species: All species
Last Modified: 2014-08-14
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.