Dual mechanisms of green tea extract (EGCG)-induced cell survival in human epidermal keratinocytes.
Beneficial effects attributed to green tea, such as its anticancer and antioxidant properties, may be mediated by (-)-epigallocatechin-3-gallate (EGCG). In this study, the effects of EGCG on cell proliferation and UV-induced apoptosis were investigated in normal epidermal keratinocytes. When topically applied to aged human skin, EGCG stimulated the proliferation of epidermal keratinocytes, which increased the epidermal thickness. In addition, this topical application also inhibited the UV-induced apoptosis of epidermal keratinocytes. EGCG was found to increase the phosphorylation of Bad protein at the Ser112 and Ser136. Moreover, EGCG-induced Erk phosphorylation was found to be critical for the phosphorylation of Ser112 in Bad protein, and the EGCG-induced activation of the Akt pathway was found to be involved in the phosphorylation of Ser136. Furthermore, EGCG increased Bcl-2 expression but decreased Bax expression, causing an increase in the Bcl-2-to-Bax ratio. In addition, we demonstrate the differential growth inhibitory effects of EGCG on cancer cells. In conclusion, this study demonstrates that EGCG promotes keratinocyte survival and inhibits the UV-induced apoptosis via two mechanisms: by phosphorylating Ser112 and Ser136 of Bad protein through Erk and Akt pathways, respectively, and by increasing the Bcl-2-to-Bax ratio. Moreover, these two proposed mechanisms of EGCG-induced cell proliferation may differ kinetically to promote keratinocyte survival.
Chung
Jin Ho
JH
Department of Dermatology, Seoul National University College of Medicine, and Laboratory of Cutaneous Aging Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
Han
Ji Hyun
JH
Hwang
Eun Ju
EJ
Seo
Jin Young
JY
Cho
Kwang Hyun
KH
Kim
Kyu Han
KH
Youn
Jai Il
JI
Eun
Hee Chul
HC
D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000078404:Epidermal Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein
C494819:BAD protein, human; C494826:BAX protein, human; D002352:Carrier Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D002392:Catechin; C045651:epigallocatechin gallate; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases