The anthocyanin metabolites gallic acid, 3-O-methylgallic acid, and 2,4,6-trihydroxybenzaldehyde decrease human colon...

Area of Science:

• Biochemistry
• Molecular Biology
• Cancer Research

Background:

• Anthocyanins, found in red grape skins, exhibit anti-cancer properties against colon cancer models.
• Gut microflora metabolize anthocyanins into phenolic acids and aldehydes, which may mediate their anti-cancer effects.
• Gallic acid (Gal), 3-O-methylgallic acid (Megal), and 2,4,6-trihydroxybenzaldehyde (THBA) were previously identified as potent Caco-2 cell viability reducers.

Purpose of the Study:

• To investigate the capacity of anthocyanin metabolites (Gal, Megal, THBA) to modulate cell cycle and induce apoptosis in colon cancer cells.
• To elucidate the mechanisms underlying the potential anti-colorectal cancer (CRC) action of these metabolites.

Main Methods:

• Caco-2 cells were incubated with varying concentrations (10-100 µM) of Gal, Megal, THBA, and malvidin-3-glucoside (M3g) for 24-72 hours.
• Cell viability, cell cycle progression (G0/G1 arrest), apoptosis (caspase-3 activation, DNA fragmentation, nuclear condensation), and transcription factor activity (NF-κB, AP-1, STAT-1, OCT-1) were assessed.

Main Results:

• Gal and Megal significantly decreased Caco-2 cell viability in a time- and dose-dependent manner.
• All tested metabolites induced cell cycle arrest at the G0/G1 phase after 72 hours.
• Megal, Gal, and THBA activated caspase-3, indicating apoptosis induction; Megal and Gal additionally caused DNA fragmentation and nuclear condensation.
• Megal, Gal, and THBA inhibited transcription factors NF-κB, AP-1, STAT-1, and OCT-1, which are implicated in CRC.

Conclusions:

• The anti-cancer effects of Megal and Gal against colon cancer cells stem from the inhibition of cell proliferation and induction of apoptosis.
• Inhibition of transcription factors crucial for cell proliferation and survival pathways contributes to the observed anti-cancer effects of these anthocyanin metabolites.