Identification of epigallocatechin-3-gallate in green tea polyphenols as a potent inducer of p53-dependent apoptosis in the human lung cancer cell line A549.
The effects of green tea polyphenols on cultured cancer cells have been well characterized, especially the effects of epigallocatechin-3-gallate (EGCg), since EGCg suppresses oncogenic signaling pathways and induces cell cycle arrest or apoptosis by regulating cell cycle-associated proteins. In the present study, we attempted to identify signaling pathways or target molecules regulated by each of or a mixture of green tea polyphenols, including epicatechin (EC), epicatechin-3-gallate (ECg), epigallocatechin (EGC), and EGCg, in the human lung cancer cell line A549. ECg, EGC, and a catechin mixture, in addition to EGCg, significantly decreased cell viability. In contrast, caspase 3/7 activity, an apoptosis indicator, was specifically induced by EGCg. By conducting a series of luciferase-based reporter assays, we revealed that the catechin mixture only up-regulates the p53 reporter. EGCg was a more potent inducer of p53-dependent transcription, and this induction was further supported by the induced level of p53 protein. RNA interference (RNAi)-mediated p53 knockdown completely abolished EGCg-induced apoptosis. Finally, a proteome and western blot analysis using approximately 70 different antibodies failed to detect up-regulated proteins in catechin mixture-treated A549 cells. Taken together, these results indicate that EGCg, among several green tea polyphenols, is a potent apoptosis inducer that functions exclusively through a p53-dependent pathway in A549 cells.
Yamauchi
Rieko
R
Department of Life Sciences, Meiji University School of Agriculture, Kawasaki, Kanagawa 214-8571, Japan.
Sasaki
Kaori
K
Yoshida
Kenichi
K
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053179:Caspase 7 / Q000187:drug effects / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D059808:Polyphenols; D015398:Signal Transduction / Q000187:drug effects; D013662:Tea / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D016159:Tumor Suppressor Protein p53; D002392:Catechin; C045651:epigallocatechin gallate; D008156:Luciferases; D053148:Caspase 3; D053179:Caspase 7