Resveratrol-induced apoptosis is associated with activation of p53 and inhibition of protein translation in T47D human breast cancer cells.
OBJECTIVE
Trans-resveratrol (RSVL; 3,4',5-trihydroxystilbene), a natural compound found in grapes, berries, peanuts and red wine exerts certain anticancer roles in different human cancer types. However, the exact molecular mechanism(s) behind such a role remains to be elucidated, thus the aim of this study.


METHODS
T47D human breast cancer cells were treated with RSVL and cell proliferation was measured by cell counting. Apoptosis was analyzed by Giemsa staining, poly(ADP-ribose) polymerase (PARP) fragmentation analysis and annexin V assay. Regulation of p53 tumor suppressor protein, p70S6K, and pS6 ribosomal protein was measured by detecting their phosphorylated active forms using ECL-immunoblot analysis.


RESULTS
The present results show that RSVL-induced growth inhibition in T47D cells is caused by apoptosis as demonstrated by morphological changes and PARP fragmentation. RSVL-induced apoptosis is associated with the activation of the p53 in a dose- and a time-dependent manner. Phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and LY294002 abolished the effect of RSVL on p53 activation. Interestingly, RSVL inhibits the expression of p70S6K and the phosphorylation of pS6RP.


CONCLUSIONS
These findings demonstrate that RSVL affects multiple intracellular signaling transduction pathways such as p53 activation/protein translation inhibition/apoptosis, and strongly support a contemplated use of this natural compound as a preventive and/or an adjuvant therapeutic drug for breast cancer. The data indicate that these proteins may be used as predictive biomarkers to evaluate the treatment efficacy of RSVL in clinical trials.
Alkhalaf
Moussa
M
Department of Biochemistry, Faculty of Medicine, Kuwait University, Kuwait, Kuwait. alkhalaf@hsc.edu.kw
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D000077185:Resveratrol; D038601:Ribosomal Protein S6 / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D038601:Ribosomal Protein S6; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D011064:Poly Adenosine Diphosphate Ribose; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D000077185:Resveratrol