title: Pro-apoptotic and anti-inflammatory properties of the green tea constituent epigallocatechin gallate increase photodynamic therapy responsiveness.
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.
authors: The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California 90027, USA.
authors: Angela
authors: A
authors: Ferrario
authors: Marian
authors: M
authors: Luna
authors: Natalie
authors: N
authors: Rucker
authors: Sam
authors: S
authors: Wong
authors: Charles J
authors: CJ
authors: Gomer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D017323:Dihematoporphyrin Ether / Q000494:pharmacology* / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism; D007249:Inflammation; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D056811:Unfolded Protein Response / Q000187:drug effects; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D017319:Photosensitizing Agents; D042442:Vascular Endothelial Growth Factors; D002392:Catechin; D017323:Dihematoporphyrin Ether; C045651:epigallocatechin gallate; D053505:Matrix Metalloproteinases, Secreted; D015232:Dinoprostone