Resveratrol induces p53 in colorectal cancer through SET7/9

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Resveratrol, a phytoalexin from red grapes and berries, shows potential as an anti-cancer agent.
• It modulates signaling pathways implicated in carcinogenesis.
• Its pro-apoptotic function in colorectal cancer warrants detailed investigation.

Purpose of the Study:

• To investigate the pro-apoptotic effects of resveratrol in colorectal cancer cell lines (HCT116, CO115, SW48).
• To elucidate the molecular mechanisms underlying resveratrol's action, focusing on tumor protein p53 (p53) and its regulatory pathways.

Main Methods:

• Assessing resveratrol's impact on colorectal cancer cell viability.
• Analyzing the expression of p53, p53 target genes (Bcl2 associated X, apoptosis regulator, Bcl2 binding component 3), SET domain containing lysine methyltransferase 7/9 (SET7/9), cleaved caspase-3, and poly (ADP-ribose) polymerases (PARP).
• Utilizing short hairpin RNA (shRNA) for genetic knockdown of SET7/9 to evaluate its role in resveratrol's effects.

Main Results:

• Resveratrol suppressed colorectal cancer cell viability.
• It enhanced the expression of p53 and its pro-apoptotic target genes.
• Resveratrol upregulated SET7/9, which positively regulates p53 stability via mono-methylation.
• Resveratrol induced apoptotic markers (cleaved caspase-3, PARP).
• SET7/9 knockdown attenuated resveratrol-induced p53, cleaved caspase-3, and PARP expression.

Conclusions:

• Resveratrol induces apoptosis in colorectal cancer cells by stabilizing p53.
• The mechanism involves SET7/9-mediated positive regulation of p53 stability.
• These findings reveal resveratrol's anti-cancer potential through p53-dependent apoptosis activation.