SICILIAN MANGO PEEL INDUCES CELLULAR STRESS ACCOMPANIED TO MITOCHONDRIAL DYSFUNCTION IN COLON CANCER CELLS

Abstract

Currently, cellular stresses as the oxidative, metabolic and genotoxic stress are considered the cause of many different human pathologies as neurodegenerative diseases (e.g.,Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis), alcoholic liver disease, chronic obstructive pulmonary disease, and also cancer. Although the role of cellular stress has been largely debated in cancer, nowadays some therapies aim to target the intracellular pro-oxidant/anti-oxidant balance triggering the tumor commitment to cell death. Therefore, it has become more necessary an improved understanding of cancer response to cellular stress that could be advantageous to develop cancer tailored therapies. In this scenario, the present study shows how extracts of some fractions of Sicilian mango, a tropical fruit rich in phytochemicals with nutraceutical properties, are able to affect the cell viability of three colon cancer cell lines (HT29, Caco2 and HCT116) inducing cellular stress. By using hydro-alcoholic extracts of three different portions of the fruit (peel, pulp and kernel), we observed that mango peel extract (MPE) is the most effective in reducing cell viability causing a remarkable LDH release and the death of all three cancer cells. The effect was accompanied by mitochondrial injury, dissipation of mitochondrial potential membrane and decrease in the level of proteins localized in the mitochondrial membrane such as voltage-dependent anion-selective channel (VDAC), mitofilin, and some members of Bcl-2 family proteins (Mcl-1, Bcl-2 and Bcl-XL). All these effects were accompanied by redox balance changes and upregulation in MnSOD, a mitochondrial scavenger enzyme able to modulate the cellular response against oxidative damage. The analysis of the effects exerted by the different phytochemicals present in MPE allowed to identify those molecules responsible for the observed anticancer effects sustaining their future employment as chemopreventive or therapeutic agents.