Resveratrol promotes apoptosis through the induction of dual specificity phosphatase 1 and sensitizes prostate cancer cells to cisplatin.

Abstract

Resveratrol is a polyphenol with chemopreventive properties against prostate cancer; however, the mechanisms underlying its actions are not completely understood. Previously, we demonstrated that DUSP1 induces apoptosis in prostate cancer cells; therefore in the present study we investigated the role of this phosphatase on resveratrol effects. Moreover, we analysed the efficiency of combined treatment of resveratrol and the chemotherapeutic drug cisplatin on cellular viability and apoptosis and its relation with DUSP1 in prostate cancer cells. We found that resveratrol up-regulates DUSP1 expression in androgen-independent prostate cancer cells, which in turn, is involved in the inhibition of the NF-κB pathway and Cox-2 expression. This phosphatase is required for the induction of apoptosis achieved by resveratrol, but does not regulate the effects of this compound on cell cycle. Furthermore, we show that resveratrol cooperates with cisplatin both in the up-regulation of DUSP1 levels and in the promotion of apoptosis, suggesting that DUSP1 is a major determinant of cisplatin sensitivity to apoptosis. These results reveal a novel molecular mechanism by which resveratrol induces apoptosis in prostate cancer cells, and highlight the importance of DUSP1 in future therapeutic approaches based in the use of this polyphenol and cisplatin.

• Authors: Desirée Martínez-Martínez, Altea Soto, Beatriz Gil-Araujo, Beatriz Gallego, Antonio Chiloeches, Marina Lasa
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 124 Pg. 273-279 (Feb 2019) ISSN: 1873-6351 [Electronic] England
• PMID: 30552915 (Publication Type: Journal Article)
• Copyright: Copyright © 2018. Published by Elsevier Ltd.

Chemical References

• Antineoplastic Agents, Phytogenic
• NF-kappa B
• Cyclooxygenase 2
• DUSP1 protein, human
• Dual Specificity Phosphatase 1
• Cisplatin
• Resveratrol

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Cisplatin (pharmacology)
• Cyclooxygenase 2 (genetics, metabolism)
• Down-Regulation
• Drug Synergism
• Dual Specificity Phosphatase 1 (genetics, metabolism)
• G2 Phase Cell Cycle Checkpoints (drug effects)
• Humans
• Male
• NF-kappa B (antagonists & inhibitors)
• PC-3 Cells
• Prostatic Neoplasms (drug therapy)
• Resveratrol (pharmacology)
• Up-Regulation