Assessing Anticancer Potential of Blueberry Flavonoids, Quercetin, Kaempferol, and Gentisic Acid, Through Oxidative Stress and Apoptosis Parameters on HCT-116 Cells

Abstract

In recent years, natural products gained popularity with their anti-inflammatory and antioxidant effects mediated by chemical compounds within their composition. Study results offering them as palliative therapy options in cancer or as anticancer agents with high levels of cytotoxicity brought a new approach to combine cancer treatment protocols with these products. From a different perspective, edible types of these products are suggested in daily diets due to their potential cancer preventive effects. Our preliminary work was on blueberry extracts (Vaccinium myrtillus) as a main representative of these natural products, and the contents of the extracts were analyzed with liquid chromatography tandem mass spectrometry (LC MS/ MS) to reveal the composition and distribution of polyphenolic compounds within. The most abundant polyphenols detected in V. myrtillus extracts were quercetin, kaempferol, and a phenolic acid, gentisic acid (GA). The compounds were further evaluated on treated HCT-116 cells for their potential anticancer effects by measuring total antioxidant status, total oxidant status, and 8hydroxydeoxyguanosine levels for evaluation of oxidative stress and through protein array analysis and flow cytometric analysis for evaluation of apoptosis. In analysis of oxidative stress parameters, reduced total oxidant levels and reduced oxidative stress index levels were found in cells treated with the compounds in comparison with untreated cells. In apoptosis-related protein profiles, at least twofold reduction in various apoptotic proteins was observed after quercetin and kaempferol treatment, whereas a different profile was observed for GA. Overall, results of this study showed that quercetin and kaempferol have strong cytotoxic, antioxidant, and apoptotic effects, although GA is mostly effective as an antioxidant polyphenol on HCT-116 cells.

Mammillaria Species—Polyphenols Studies and Anti-Cancer, Anti-Oxidant, and Anti-Bacterial Activities

“…Gentisic acid is a quinonoid phenolic acid that is important for cancer prevention and treatment. These phenols activate the brain chemotherapeutics that help in the reduction of brain tumors [33] and has anti-oxidant activities related to the control of HCT-116 cancer cells [34]. In M. muehlenpfordtii there were strong antiproliferative activities against different cancer cells, which is explained by the activity of the major phenol found, which is chlorogenic acid.…”

Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer

“…The anticancer effectiveness of Vaccinium myrtillus whole extract on HCT-116 cells, demonstrated to be an effective antioxidant. It is worth mentioning that GeA is considered to be one of the most abundant polyphenols found in this extract along with quercetin and kaempferol [16].…”

Saudi Rosmarinus officinalis and Ocimum basilicum L. Polyphenols and Biological Activities

“…Polyphenols activate the detoxification enzymes and reduce free radicals [4,9]. The antiproliferative and apoptotic activities of polyphenols against cancer cells is attributed to the control of cell cycle arrest, as well as the molecular regulation of cancer related genes [4,[9][10][11].…”