Resveratrol prevents p53 core domain aggregation (754.1)

Abstract

p53 has an essential role in preventing cancer development by inducing cell cycle arrest and/or apoptosis in response to cellular stress. Mutations in the p53 gene are described in over 50% of all human cancers. Besides the mutations, cellular aggregation of p53 can also inactivate the protein, leading to malignancy. Resveratrol, a natural polyphenol found in grapes and red wine, is able to induce p53‐dependent cell death in a variety of cell lines. Although several indirect mechanisms of p53 activation by resveratrol have been proposed, there is no evidence that this bioactive compound can interact with p53. Thus, we investigated a possible interaction between resveratrol and the p53 core domain (p53C). In addition, we tested the potential of resveratrol in preventing wild‐type and mutated p53 aggregation in vitro and in tumor cells. Experiments were performed by using fluorescence spectroscopy and fluorescence microscopy techniques. Our data suggest that an interaction between resveratrol and the wild‐type p53C does occur. We also found that resveratrol has the ability to inhibit the wild‐type p53 core domain as well as the R248Q p53 mutant to undergo in vitro aggregation. Additionally, resveratrol (50 and 100µM) reduces the formation of nuclear p53 aggregates in MDA‐MB231 human breast cancer cells. Our study provides evidence that resveratrol can directly modulate p53 and may pave the way for a better understanding of the mechanisms involved in p53 protein aggregation as a therapeutic strategy for cancer treatment.Grant Funding Source: Supported by FAPERJ, CNPq, INCT/INBEB