Antitumor effect of green tea polyphenol epigallocatechin-3-gallate in ovarian carcinoma cells: evidence for the endothelin-1 as a potential target.
The green tea polyphenol, epigallocatechin-3-gallate (EGCG), has been shown to prevent cancer; however, a precise mechanism responsible for tumor growth inhibition has not yet been clearly described. The endothelin (ET) A receptor (ET(A)R)/ET-1 autocrine pathway is overexpressed in ovarian carcinoma and triggers tumor growth, neoangiogenesis, and invasion. These latter tumor-promoting effects are mediated through the activation of cyclooxygenase (COX)-1- and COX-2-dependent pathways by ET-1. In the present study, pretreatment of HEY and OVCA 433 ovarian carcinoma cell lines with green tea and EGCG inhibited ET-1/ET(A)R expression, ET(A)R-mediated COX-1/2 mRNA expression, and COX-2 promoter activity. These effects were associated with a significant reduction in the COX-1/2-derived prostaglandin E2 (PGE2) production. These results provide a novel insight into the mechanism by which EGCG, by affecting ET(A)R-dependent COX-1/2 pathways may inhibit ovarian tumors suggesting that EGCG may be useful in preventing and treating ovarian carcinoma in which activation of ET(A)R by ET-1 plays a critical role in tumor growth and progression.
Spinella
Francesca
F
Molecular Pathology and UltrastructureLaboratory, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy.
Rosanò
Laura
L
Decandia
Samantha
S
Di Castro
Valeriana
V
Albini
Adriana
A
Elia
Giacomo
G
Natali
Pier Giorgio
PG
Bagnato
Anna
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013662:Tea / Q000737:chemistry*
D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D012333:RNA, Messenger; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D015232:Dinoprostone