Green tea extract enhances the selective cytotoxic activity of Zizyphus jujuba extracts in HepG2 cells.
Anticarcinogenic effects attributed to phytochemicals may be based on synergistic, additive, or antagonistic interactions of many compounds. In our previous study, we demonstrated that the chloroform fraction (CHCl(3)-F) from Z. jujuba has anticancer activity in HepG2 cells. In China, many people drink jujuba tea and believe in the synergic effects of jujuba and tea for better health. We therefore investigated the effects of CHCl(3)-F and green tea extract (GTE), and their underlying mechanisms of action in HepG2 cells. Our results showed that GTE enhanced the effect of CHCl(3)-F on cell viability in HepG2 cells, without cytotoxicity in rat hepatocytes, which was used as a normal cell model. Furthermore, combination of CHCl(3)-F and GTE caused an effect on G1 phase arrest but not on apoptosis. Interestingly, the mechanism of the G1 arrest was associated, not with an increase in p27(Kip1) levels and the hypohosphorylation of Rb, which are pathways used by CHCl(3)-F on G1 arrest in HepG2 cells, but with increases in p53 and p21(Waf1/Cip1) levels, and a decrease in cyclin E levels. Collectively, our findings suggest that combination of CHCl(3)-F and GTE produces an enhanced cell growth inhibition effect, and that the resultant G1 arrest was caused via a different mechanism as that of CHCl(3)-F treatment alone.
Huang
Xuedan
X
Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka 558-8585, Japan.
Kojima-Yuasa
Akiko
A
Xu
Shenghui
S
Norikura
Toshio
T
Kennedy
David Opare
DO
Hasuma
Tadayoshi
T
Matsui-Yuasa
Isao
I
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D028241:Camellia sinensis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019927:Cyclin E / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D013662:Tea; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D031957:Ziziphus
C493958:Cdkn1a protein, rat; C493962:Cdkn1b protein, rat; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004365:Drugs, Chinese Herbal; D017382:Reactive Oxygen Species; D016160:Retinoblastoma Protein; D013662:Tea; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004247:DNA