Mechanism by Which Cyanidin-3-O-glucoside and Its Metabolite Protocatechuic Acid Repair Heterocyclic Aromatic Amines-induced Cell Damage

To study the potential mechanism of action of cyanidin-3-O-glucoside (C3G) and its main metabolite protocatechuic acid (PCA) in repairing heterocyclic aromatic amine-induced cell damage.

2-Amino-3-methylimidazolidine[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-imidazole[4,5-b]pyridine (PhIP) were used separately to induce cell damage to HepG2 cells. The cell counting kit-8 (CCK-8) assay, Hoechst33258 staining, flow cytometry and fluorescence quantitative polymerase chain reaction (qPCR) were used to evaluate the effects of C3G and PCA on the cell survival and cell cycle as well as the expression of key genes associated with cell apoptosis and DNA damage in heterocyclic aromatic amine-damaged cells.

C3G and PCA significantly increased the cell viability of heterocyclic aromatic amine-damaged HepG2 cells and induced S phase arrest. Compared with the IQ group, C3G and PCA significantly reduced the mRNA expression of GADD45α and the pro-apoptotic gene Bim, and increased the mRNA expression of the anti-apoptotic genes Bcl-2 and Bcl-xl (P < 0.05). Compared with the PhIP group, C3G and PCA could promote the expression of most pro-apoptotic genes.

C3G and PCA can repair cell damage induced by IQ and PhIP through reducing DNA damage and cell apoptosis. However, when cell damage is too severe to be reversed, they can instead promote cell apoptosis, thus reducing canceration.