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Selective proapoptotic activity of polyphenols from red wine on teratocarcinoma cell, a model of cancer stem-like
Tanveer Sharif1, Cyril Auger, Christian Bronner
1UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Université de Strasbourg, B.P. 60024, Illkirch, 67401, France.
Abstract:
Cancer stem cells are expected to be responsible for tumor initiation and metastasis. These cells are therefore potential targets for innovative anticancer therapies. However, the absence of bona fide cancer stem cell lines is a real problem for the development of such approaches. Since teratocarcinoma cells are totipotent stem cells with a high degree of malignancy, we used them as a model of cancer stem cells in order to evaluate the anticancer chemopreventive activity of red wine polyphenols (RWPs) and to determine the underlying cellular and molecular mechanisms. We therefore investigated the effects of RWPs on the embryonal carcinoma (EC) cell line P19 which was grown in the same culture conditions as the most appropriate normal cell line counterpart, the pluripotent embryonic fibroblast cell line NIH/3T3. The present study indicates that RWPs selectively inhibited the proliferation of P19 EC cells and induced G1 cell cycle arrest in a dose-dependent manner. Moreover, RWPs treatment specifically triggered apoptosis of P19 EC cells in association with a dramatic upregulation of the tumor suppressor gene p53 and caspase-3 activation. Our findings suggest that the chemopreventive activity of RWPs on tumor initiation and development is related to a growth inhibition and a p53-dependent induction of apoptosis in teratocarcinoma cells. In addition, this study also shows that the EC cell line is a convenient source for studying the responses of cancer stem cells to new potential anticancer agents.
Insights
Red wine polyphenols (RWPs) show anticancer potential by inhibiting cancer stem cell proliferation and inducing apoptosis. This study highlights RWPs
Area of Science:
- * Cancer Biology
- * Pharmacology
- * Molecular Oncology
Background:
- * Cancer stem cells (CSCs) drive tumor initiation and metastasis, making them key therapeutic targets.
- * Lack of reliable CSC models hinders the development of novel anticancer therapies.
- * Teratocarcinoma cells, as malignant totipotent stem cells, serve as a valuable model for CSC research.
Purpose of the Study:
- * To evaluate the chemopreventive activity of red wine polyphenols (RWPs) on cancer stem cells.
- * To elucidate the cellular and molecular mechanisms underlying RWPs' effects.
- * To validate embryonal carcinoma (EC) cell lines as a model for CSC drug screening.
Main Methods:
- * Investigated RWPs' effects on the P19 embryonal carcinoma (EC) cell line, a CSC model.
- * Utilized NIH/3T3 fibroblasts as a normal cell counterpart for comparative analysis.
- * Analyzed cell proliferation, cell cycle progression (G1 arrest), apoptosis, p53 gene expression, and caspase-3 activation.
Main Results:
- * RWPs selectively inhibited P19 EC cell proliferation in a dose-dependent manner.
- * RWPs induced G1 cell cycle arrest in P19 EC cells.
- * RWPs triggered apoptosis in P19 EC cells, associated with p53 upregulation and caspase-3 activation.
Conclusions:
- * RWPs exhibit chemopreventive activity against tumor initiation and development by inhibiting CSC proliferation and inducing apoptosis.
- * The observed effects are mediated through a p53-dependent apoptotic pathway in teratocarcinoma cells.
- * EC cell lines are suitable models for studying CSC responses to potential anticancer agents.
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