Stabilization of p53 is involved in quercetin-induced cell cycle arrest and apoptosis in HepG2 cells

Area of Science:

• Molecular Biology
• Biochemistry
• Cancer Research

Background:

• Defects in p53 activation mechanisms are common in cancers with wild-type p53.
• Reactivating p53 is a promising strategy for treating these tumors.

Purpose of the Study:

• To investigate the potential of quercetin, a plant flavonoid, to reactivate wild-type p53 in HepG2 liver cancer cells.
• To elucidate the molecular mechanisms underlying quercetin's effects on p53 and cancer cell behavior.

Main Methods:

• HepG2 cells were treated with quercetin.
• Cell proliferation, cell cycle distribution, and apoptosis were analyzed.
• Western blotting was used to assess p53 phosphorylation, total p53, p21, cyclin D1, Bax, and Bcl-2 protein levels.
• p53 mRNA levels and degradation were examined.
• p53 ubiquitination and half-life were measured.
• p53 was silenced using small interfering RNA (siRNA).

Main Results:

• Quercetin inhibited HepG2 cell proliferation by inducing cell cycle arrest and apoptosis.
• Quercetin increased p53 phosphorylation and total p53 protein levels without affecting p53 mRNA transcription.
• Quercetin modulated downstream targets, increasing p21 and Bax/Bcl-2 ratio, while decreasing cyclin D1.
• Quercetin inhibited p53 ubiquitination, extended p53 half-life, and reduced p53 mRNA degradation.
• p53 silencing abrogated quercetin's effects on gene expression and apoptosis.

Conclusions:

• Quercetin reactivates p53 in HepG2 cells by stabilizing p53 at both mRNA and protein levels.
• This stabilization leads to p53-dependent cell cycle arrest and apoptosis, suggesting quercetin as a potential therapeutic agent for wild-type p53 cancers.