Resveratrol prevents p53 aggregation in vitro and in breast cancer cells

Area of Science:

• Biochemistry
• Molecular Biology
• Cancer Therapeutics

Background:

• The tumor suppressor p53 (protein 53) is frequently mutated in over 50% of human cancers.
• Mutations in p53 can lead to loss of function, dominant negative effects, and gain of function, often associated with amyloid aggregation.
• Targeting p53 aggregation presents a potential therapeutic avenue for cancer treatment.

Purpose of the Study:

• To investigate the interaction between resveratrol and wild-type and mutant p53 (protein 53).
• To evaluate resveratrol's potential to inhibit p53 aggregation in vitro and in human breast cancer cells.
• To assess the impact of resveratrol on cancer cell proliferation and migration.

Main Methods:

• Fluorescence spectroscopy was used to study the interaction between resveratrol and p53 core domain (p53C) in vitro.
• Immunofluorescence co-localization assays were performed in human breast cancer cell lines (MDA-MB-231, HCC-70, MCF-7).
• Cell proliferation and migration assays were conducted using MDA-MB-231 cells.

Main Results:

• Resveratrol directly interacts with the wild-type p53 core domain (p53C).
• Resveratrol, pterostilbene, and piceatannol inhibited mutant p53C aggregation in vitro.
• Resveratrol reduced mutant p53 protein aggregation in MDA-MB-231 and HCC-70 cells, but not in MCF-7 cells.
• Resveratrol significantly decreased cell proliferation and migration in MDA-MB-231 cells.

Conclusions:

• Resveratrol directly modulates p53 (protein 53) activity and aggregation.
• Resveratrol demonstrates potential as a therapeutic agent by inhibiting p53 aggregation and reducing cancer cell tumorigenicity.
• This study enhances understanding of p53 aggregation mechanisms and its therapeutic implications.