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Resveratrol suppresses cell transformation and induces apoptosis through a p53-dependent pathway
1The Hormel Institute, University of Minnesota, Austin 55912, USA.
Abstract:
Resveratrol, a plant constituent enriched in the skin of grapes, is one of the most promising agents for the prevention of cancer. However, the mechanism of the anti-carcinogenic activity of resveratrol is not well understood. Here we offer a possible explanation of its anti-cancer effect. Resveratrol suppresses tumor promoter-induced cell transformation and markedly induces apoptosis, transactivation of p53 activity and expression of p53 protein in the same cell line and at the same dosage. Also, resveratrol-induced apoptosis occurs only in cells expressing wild-type p53 (p53+/+), but not in p53-deficient (p53-/-) cells, while there is no difference in apoptosis induction between normal lymphoblasts and sphingomyelinase-deficient cell lines. These results demonstrate for the first time that resveratrol induces apoptosis through activation of p53 activity, suggesting that its anti-tumor activity may occur through the induction of apoptosis.
Insights
Resveratrol, found in grapes, shows anti-cancer promise. It induces apoptosis, or programmed cell death, by activating p53, a key tumor suppressor protein, offering a new understanding of its cancer-preventive effects.
Area of Science:
- Molecular Biology
- Cancer Research
- Pharmacology
Background:
- Resveratrol, a natural compound from grapes, is recognized for its potential anti-cancer properties.
- The precise mechanisms underlying resveratrol's anti-carcinogenic effects remain incompletely understood.
- Understanding these mechanisms is crucial for developing effective cancer prevention strategies.
Purpose of the Study:
- To elucidate the mechanism by which resveratrol exerts its anti-cancer effects.
- To investigate the role of p53 in resveratrol-mediated apoptosis.
- To explore the relationship between resveratrol, p53 activity, and cancer cell death.
Main Methods:
- Utilized cell lines with varying p53 expression levels (wild-type p53+/+ and p53-deficient p53-/-).
- Assessed the impact of resveratrol on tumor promoter-induced cell transformation.
- Quantified apoptosis, p53 activity, and p53 protein expression following resveratrol treatment.
Main Results:
- Resveratrol suppressed tumor promoter-induced cell transformation.
- Resveratrol significantly induced apoptosis, p53 activity, and p53 protein expression.
- Resveratrol-induced apoptosis was observed exclusively in cells with wild-type p53, but not in p53-deficient cells.
- Apoptosis induction by resveratrol was independent of sphingomyelinase deficiency.
Conclusions:
- Resveratrol induces apoptosis through the activation of p53.
- The anti-tumor activity of resveratrol may be mediated by p53-dependent apoptosis.
- This study provides a mechanistic explanation for resveratrol's potential as a cancer-preventive agent.