Candice Mazewski1, Elvira Gonzalez de Mejia1, Qian Li1, Megan West2, Leslie West1, and Katie Liang3
1Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign
2The Kraft Heinz Company, Glenview, IL
3Department of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign
Anthocyanins, which can be utilized as natural pigments in food products, have been shown to provide various health benefits. The objective was to evaluate the anti-proliferative effect of anthocyanin rich extracts of purple and red corn on HCT116 and HT-29 human colorectal cancer cells in comparison to oxaliplatin and to investigate the mechanism of action. Four extracts in this study included red corn acidified water extract (RAW), purple corn acidified water extract (PAW), PAW with additional ethyl acetate purification (PAWE), and purple corn pericarp water extract (PW). Analyses were conducted in at least two independent replicates and statistical differences were determined by Tukey-Kramer analysis (p<0.05). Total monomeric anthocyanin concentrations for the extracts were 56.2±1.3a, 190.0±3.3c, 217.5±6.3d, and 92.3±1.8b mg cyanindin-3-glucoside equivalent per g extract, respectively. IC50 values for RAW, PAW, PAWE, and PW on HT-29 cells were 2.5±0.2b, 3.4±0.1b, 5.6±0.4a, and 6.3±0.2a mg/mL, and on HCT116 cells were 1.1±0.1c, 2.5±0.2b, 2.3±0.1b, and 3.5±0.0a mg/mL, respectively, suggesting corn anthocyanin extracts exhibited anti-proliferative effects on colon cancer cells. Cytotoxicity of PW was tested on normal colon cells and no significant inhibition was seen at 10 mg/mL. Extracts were tested on several apoptosis markers to determine the possible mechanisms in which they inhibit proliferation. All extracts exhibited an increased BAX/Bcl-2 ratio and increased Cytochrome-C expression in comparison to the untreated cells, which determined apoptotic potential of the extracts. The effect of anthocyanin extracts to act as tyrosine kinase inhibitors (TKI) was assessed because TKI play a role in preventing tumor angiogenesis and cell proliferation. Free energy of binding of the main anthocyanins from corn, including cyanidin-3-O-glucoside (C3G), pelargonidin-3-O-glucoside (Pr3G), and peonidin-3-O-glucoside (Pn3G), to tyrosine kinase proteins was estimated through docking experiments. Free energy of binding of C3G, Pr3G, and Pn3G to a receptor tyrosine kinase were -7.18, -5.98, and -6.81 kcal/mol, and to a non-receptor tyrosine kinase were -7.86, -7.71, and -6.69, respectively, indicating anthocyanins present in the corn extracts have an affinity to inhibit tyrosine kinases. The results suggest that corn anthocyanin extracts may suppress colon cancer cell proliferation through apoptotic pathways and by acting as tyrosine kinase inhibitors.