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Induction of p57 is required for cell survival when exposed to green tea polyphenols
Stephen Hsu1, Fu-Shin Yu, Jill Lewis
1Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, AD1443, Medical College of Georgia, Augusta, GA 30912-1126, USA. shsu@mail.mcg.edu
Abstract:
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.
Insights
Green tea polyphenols induce cell death in tumor cells. Normal cells survive by upregulating p57/KIP2, a protein protecting them from polyphenol-induced apoptosis.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Green tea polyphenols (catechins) exhibit anti-tumor properties by inducing apoptosis in cancer cells.
- The mechanism by which normal epithelial cells evade polyphenol-induced cell death remains unclear.
- Previous research identified p57/KIP2 as a protein induced by green tea polyphenols specifically in normal human epithelial cells.
Purpose of the Study:
- To investigate the role of p57/KIP2 in normal epithelial cell survival amidst green tea polyphenol exposure.
- To elucidate the correlation between p57 expression levels and the induction of apoptosis.
Main Methods:
- Western blot analysis to assess protein expression levels.
- Caspase 3 assays to quantify apoptotic activity.
- Morphological analysis to observe cellular changes.
- Retroviral transfection to overexpress p57 in cancer cells.
Main Results:
- Green tea polyphenols triggered apoptosis in cells lacking p57 induction via Apaf-1 and caspase 3 activation.
- Cells with inducible p57 maintained low Apaf-1 and proliferating cell nuclear antigen (PCNA) levels, with basal caspase 3 activity.
- p57-expressing oral carcinoma cells demonstrated significant resistance to green tea polyphenol-induced apoptosis.
Conclusions:
- p57/KIP2 acts as a crucial pro-survival factor, protecting normal epithelial cells from green tea polyphenol-induced apoptosis.
- The induction of p57 is a key mechanism for normal cell survival in the presence of potent anti-cancer compounds found in green tea.