Resveratrol prevents p53 aggregation in vitro and in breast cancer cells
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Danielly C. Ferraz da Costa1,2, Nathali P.C. Campos2,3, Ronimara A. Santos1, Francisca Hildemagna Guedes-da-Silva2,3, Mafalda Maria D.C. Martins-Dinis2,3, Letícia Zanphorlin4, Carlos Ramos4, Luciana P. Rangel2,5 and Jerson L. Silva2,3
1Departamento de Nutrição Básica e Experimental, Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-013, RJ, Brazil
2Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
3Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
4Instituto de Química, Universidade de Campinas, Campinas 13083-970, SP, Brazil
5Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
Jerson L. Silva, email: email@example.com
Keywords: amyloid aggregation; p53; cancer; aggregation; resveratrol
Received: June 22, 2017 Accepted: June 04, 2018 Published: June 26, 2018
One potential target for cancer therapeutics is the tumor suppressor p53, which is mutated in more than 50% of malignant tumors. Loss of function (LoF), dominant negative (DN) and gain of function (GoF) mutations in p53 are associated with amyloid aggregation. We tested the potential of resveratrol, a naturally occurring polyphenol, to interact and prevent the aggregation of wild-type and mutant p53 in vitro using fluorescence spectroscopy techniques and in human breast cancer cells (MDA-MB-231, HCC-70 and MCF-7) using immunofluorescence co-localization assays. Based on our data, an interaction occurs between resveratrol and the wild-type p53 core domain (p53C). In addition, resveratrol and its derivatives pterostilbene and piceatannol inhibit mutant p53C aggregation in vitro. Additionally, resveratrol reduces mutant p53 protein aggregation in MDA-MB-231 and HCC-70 cells but not in the wild-type p53 cell line MCF-7. To verify the effects of resveratrol on tumorigenicity, cell proliferation and cell migration assays were performed using MDA-MB-231 cells. Resveratrol significantly reduced the proliferative and migratory capabilities of these cells. Our study provides evidence that resveratrol directly modulates p53, enhancing our understanding of the mechanisms involved in p53 aggregation and its potential as a therapeutic strategy for cancer treatment.
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