Cellular thiol status-dependent inhibition of tumor cell growth via modulation of retinoblastoma protein phosphorylation by (-)-epigallocatechin.
Tea polyphenols have been shown to inhibit tumor cell growth, but there is limited information on their effects on cell signaling and cell cycle control pathways. We have shown the involvement of such mechanisms as activation of mitogenic activated protein kinases, decreases in ornithine decarboxylase activity and in cellular thiol levels, elicitation of mitochondrial cytochrome c release, and activation of caspases by the green tea galloyl polyphenol, epigallocatechin (EGC). In the current study, we sought to determine how EGC alters cell cycle and its related control factors in its growth inhibitory effect in Ehrlich ascites tumor cells. The significant finding here is that EGC caused a dose-dependent accumulation of cells in the G1 phase and a decrease in the phosphorylation of the retinoblastoma (Rb) protein, which was also in a cellular thiol-dependent manner. The involvement of a cellular thiol-dependent modulation in Rb phosphorylation leading to the regulation of tumor cell growth by a green tea polyphenol is a novel observation, to the best of our knowledge.
Kennedy
David Opare
DO
Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.
Kojima
Akiko
A
Moffatt
Jerry
J
Yamagiwa
Hitoshi
H
Yano
Yoshihisa
Y
Hasuma
Tadayoshi
T
Otani
Shuzo
S
Matsui-Yuasa
Isao
I
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013662:Tea; D014407:Tumor Cells, Cultured
D010936:Plant Extracts; D016160:Retinoblastoma Protein; D013438:Sulfhydryl Compounds; D013662:Tea; D002392:Catechin; C057580:gallocatechol