Flavonoids regulate cell death-related cellular signaling via ROS in human colon cancer cells

[Display omitted] •Catechins and naringenin showed considerable cytotoxicity in colon cancer cells.•Catechins and naringenin induce cell death via upregulation of cell death-related genes.•The pro-apoptotic and autophagic activity of catechins and naringenin was ROS dependent.•Catechin and naringenin induce G2/M cell cycle arrest in cancer cells.•Catechins and naringenin can suppress overexpressed CAMs in colon cancer cells. Although several studies investigated effects of flavonoids on proliferation and apoptosis, yet no study has correlated the cellular damage caused by reactive oxygen species (ROS) production, cell death related pathways and cell adhesion molecules (CAM) expression with cell survival. Here, we investigate cytotoxic effect of catechin, epicatechin and naringenin on colon cancer cells. While especially naringenin demonstrated most significant inhibition of colon cancer cell viability, high concentrations treatment did not exhibit more pronounced effect in colon epithelial cells. In addition, these flavonoids caused excessive ROS generation resulting in the impairment of lipid and protein, followed by the induction of apoptosis and autophagy. In details, mechanism studies revealed that elevated ROS production leads to caspase activation and pretreated NAC, an antioxidant, blocks catechins and naringenin induced apoptosis and autophagy. PKC activity assay data also showed that catechin and naringenin treatment decreases PKC activity that leads to cell death. Moreover, studied flavonoids, especially naringenin, induced G2/M cell cycle arrest in a ROS-independent manner. Furthermore, the studied flavonoids suppressed or decreased the expression of the cancer progression and metastasis-related cell adhesion molecules. Taken together, our results indicate that studied flavonoids suppress colon cancer cell growth via inducing cell death in ROS dependent manner.