Journal
CANCER LETTERS
Volume 289, Issue 2, Pages 188-194Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2009.08.015
Keywords
Photodynamic therapy (PDT); Apoptosis; Hsp-90; 17-AAG; Geldanamycin
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Funding
- NIH [RO1 CA31230, RO1 CA119907]
- Martell Foundation for Leukemia, Cancer, and Aids Research
- Las Madrinas Endowment for Experimental Therapeutics
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The geldanamycin derivative, 17-allylamino-17-demethoxygeldanamycin (17-AAG), binds to the amino-terminal ATP binding pocket of the 90 kDa heat shock protein (Hsp-90) and inhibits this chaperone from stabilizing client proteins involved with the malignant phenotype. We examined the effects of a combined modality protocol involving photodynamic therapy (PDT) and 17-AAG in mouse mammary carcinoma cells and tumors. PDT increased the expression of the anti-apoptotic and pro-angiogenic proteins survivin, Akt, HIF-1 alpha, MMP-2 and VEGF in tumor tissue and this expression decreased significantly when 17-AAG was included in the treatment regimen. Tumor bearing mice treated with PDT and 17-AAG had improved long-term tumoricidal responses when compared with individual treatment protocols. We conclude that Hsp-90 plays an active role in modulating tumor responsiveness following PDT and targeting Hsp-90 with 17-AAG enhances the therapeutic effectiveness of PDT. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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