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Lasers Surg Med. 2011 Sep;43(7):644-50. doi: 10.1002/lsm.21081.

Pro-apoptotic and anti-inflammatory properties of the green tea constituent epigallocatechin gallate increase photodynamic therapy responsiveness.

Author information

1
The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California 90027, USA.

Abstract

BACKGROUND:

A polyphenol constituent of green tea, epigallocatechin gallate (EGCG), has anti-carcinogenic properties. A growing number of studies document EGCG-mediated 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 pro-survival 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 pro-survival proteins GRP-78 and survivin, and attenuated PDT-induced prostaglandin E2 (PGE2 ) expression in PDT-treated 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.

PMID:
22057492
PMCID:
PMC3211098
DOI:
10.1002/lsm.21081
[Indexed for MEDLINE]
Free PMC Article
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