Berry anthocyanins reduce proliferation of human colorectal carcinoma cells by inducing caspase-3 activation and p21 upregulation

Abstract

Colorectal cancer is the fourth most common type of cancer worldwide, and adenocarcinoma cells that form the majority of colorectal tumors are markedly resistant to antineoplastic agents. Epidemiological studies have demonstrated that consumption of fruits and vegetables that are rich in polyphenols, is linked to reduced risk of colorectal cancer. In the present study, the effect of a standardized anthocyanin (ACN)-rich extract on proliferation, apoptosis and cell cycle in the Caco-2 human colorectal cancer cell line was evaluated by trypan blue and clonogenic assays and western blot analysis of cleaved caspase-3 and p21Waf/Cif1. The results of the current study demonstrated that the ACN extract markedly decreased Caco-2 cell proliferation, induced apoptosis by activating caspase-3 cleavage, and upregulated cyclin-dependent kinase inhibitor 1 (p21Waf/Cif1) expression in a dose dependent manner. Furthermore, ACN extract was able to produce a dose-dependent increase of intracellular reactive oxygen species (ROS) in Caco-2 cells, together with a light increase of the cell total antioxidant status. In conclusion, the present study demonstrated that a standardized berry anthocyanin rich extract inhibited proliferation of Caco-2 cells by promoting ROS accumulation, inducing caspase-3 activation, and upregulating the expression of p21Waf/Cif1.