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Cellular insights into the role of resveratrol on p53 modulation
Author(s) -
Costa Danielly Cristiny Ferraz,
Malheiros Maitê Santos,
Sanches Daniel,
Casanova Fabiana Alves,
Fialho Eliane,
Silva Jerson Lima
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.764.2
Resveratrol (RV), a dietary bioactive compound found in grapes and red wine, is a promising chemopreventive agent and has the tumor suppressor protein p53 as one of its major cellular targets. Thus, the aim of this study is to investigate the effects of RV on breast cancer cells (MCF‐7), that constitutively express p53, and on non‐small lung cancer cells (H1299), which have a partial deletion of this protein‐encoding gene. Cell viability assays revealed that RV (0–500 μM) exerted a cytotoxic effect on MCF‐7 and this effect was partially mediated by p53. Treatment with RV (0–200 μM) also promoted a significant increase in p53 protein levels in MCF‐7, without altering p53 mRNA levels, thus suggesting a possible modulation of this protein by post‐translational processes. Under these experimental conditions, RV increased p21 and phospho‐Chk2 levels and stimulated PARP cleavage, which was accompanied by activation of caspases 7 and 9. On the other hand, RV was less cytotoxic to H1299 cells, which do not express p53. However, these cells became more sensitive to RV‐induced cell death when transfected with a p53‐GFP plasmid. Thus, our results suggest that the citotoxicity promoted by RV in tumor cells requires p53 function and the modulation of this protein by this bioactive compound seems to be an important mechanism by which RV exerts its chemopreventive effects. Financial Support: INBEB, FAPERJ, FAF and CNPq.