Pro-apoptotic and anti-inflammatory properties of the green tea constituent epigallocatechin gallate increase photodynamic therapy responsiveness
✍ Scribed by Angela Ferrario; Marian Luna; Natalie Rucker; Sam Wong; Charles J. Gomer
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 403 KB
- Volume
- 43
- Category
- Article
- ISSN
- 0196-8092
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✦ Synopsis
Background: A polyphenol constituent of green tea, epigallocatechin gallate (EGCG), has anti-carcinogenic properties. A growing number of studies document EGCGmediated induction of apoptotic pathways and inhibition of pro-survival factors when combined with chemotherapy or radiation. We evaluated the efficacy of EGCG in modulating photofrin (PH)-mediated photodynamic therapy (PDT) responses. Methods: Mouse mammary carcinoma (BA) cells and transplanted BA tumors growing in C3H mice were treated with PH-mediated PDT. Select groups of treated cells and mice also received EGCG and then cytotoxicity, tumor response, and expression of survival molecules were evaluated in all experimental groups. Results: EGCG increased apoptosis and cytotoxicity in BA cells exposed to PH-mediated PDT. The initial prosurvival phase of the unfolded protein response (UPR), characterized by increased expression of the 78 kDa glucose-regulated protein (GRP-78), was induced by PDT. The second pro-apoptotic phase of the UPR, characterized by phospho-c-Jun N-terminal kinase (p-JNK) expression, activation of caspases-3 and 7, poly ADP ribose polymerase (PARP) cleavage, and expression of C/EBP homologous protein was observed when PDT was combined with EGCG. EGCG also decreased the expression of the prosurvival proteins GRP-78 and survivin, and attenuated PDT-induced prostaglandin E 2 (PGE 2 ) expression in PDTtreated cells. Comparable responses also were observed when BA tumors were treated with PDT and EGCG. In addition, PDT-induced expression of metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) was down-regulated in treated tumor tissue by EGCG. Conclusions: The polyphenol EGCG improves PDT efficacy by increasing tumor apoptosis and decreasing expression of pro-survival and angiogenic molecules within the tumor microenvironment. Lasers Surg. Med. 43:644-650, 2011.