Induction of p57 is required for cell survival when exposed to green tea polyphenols.
Green tea polyphenols (catechins) are known to induce cell death in many types of tumor cells, but how normal epithelial cells survive in the presence of polyphenols is unknown. We recently reported that green tea polyphenols potently induced a cyclin-dependent kinase inhibitor, p57/(KIP2), only in normal human epithelial cells. In this study, we investigated the correlation between p57 expression and survival/apoptosis by Western blot analysis, caspase 3 assays and morphological analysis. It was demonstrated that, in the cells that lack p57 induction, green tea polyphenols induced Apaf-1 expression along with caspase 3 activation, leading to apoptosis. In contrast, cells with polyphenol-inducible p57 maintained constant levels of Apaf-1 and proliferating cell nuclear antigen (PCNA), with basal caspase 3 activity. Retroviral-transfected, p57-expressing oral carcinoma cells showed significant resistance to green tea polyphenol-induced apoptosis. Our results suggest that p57/KIP2 is a determinant pro-survival factor for cell protection from green tea polyphenol-induced apoptosis.
Hsu
Stephen
S
Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, AD1443, Medical College of Georgia, Augusta, GA 30912-1126, USA. shsu@mail.mcg.edu
Yu
Fu-Shin
FS
Lewis
Jill
J
Singh
Baldev
B
Borke
James
J
Osaki
Tokio
T
Athar
Mohammad
M
Schuster
George
G
D017209:Apoptosis / Q000187:drug effects; D053477:Apoptotic Protease-Activating Factor 1; D001940:Breast / Q000166:cytology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D013662:Tea; D014162:Transfection
C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases