Abstract
Ethanolic extracts from Mangifera indica L. have been proved to possess anti-tumor properties in many cancer systems. However, although most effects have been demonstrated with fruit pulp extract, the underlying molecular mechanisms of mango peel are still unclear. This study was designed to explore the effects of mango peel extract (MPE) on colon cancer cell lines. MPE affected cell viability and inhibited the colony formation trend of tumor cells, while no effects were observed in human dermal fibroblasts used as a non-cancerous cell line model. These events were a consequence of the induction of apoptosis associated to reactive oxygen species (ROS) production, activation of players of the oxidative response such as JNK and ERK1/2, and the increase in Nrf2 and manganese superoxide dismutase (MnSOD). Significantly, mango peel-activated stress triggered a DNA damage response evidenced by the precocious phosphorylation of histone 2AX (γH2AX), as well as phosphorylated Ataxia telangiectasia-mutated (ATM) kinase and p53 upregulation. Mango peel extract was also characterized, and HPLC/MS (High Performance Liquid Chromatography/Mass Spectrometry) analysis unveiled the presence of some phenolic compounds that could be responsible for the anti-cancer effects. Collectively, these findings point out the importance of the genotoxic stress signaling pathway mediated by γH2AX in targeting colon tumor cells to apoptosis.
Highlights
In recent years, many different findings have highlighted the beneficial value of food in the prevention and/or as a supportive strategy of the most common therapies for the treatment of many chronic diseases [1]
The pulp is endowed with a high polyphenolic and carotenoid content represented by mangiferin, gallic acid, gallotannins, quercetin, isoquercetin, ellagic acid, β-glucogallin and α- and β-carotene, many studies have supported the relevant composition of the other parts of mango fruit
Our study demonstrates for the first time that mango peel induces a selective mechanism of apoptotic cell death on colon cancer cells and that this effect is related to γH2AX-mediated genotoxic stress
Summary
Many different findings have highlighted the beneficial value of food in the prevention and/or as a supportive strategy of the most common therapies for the treatment of many chronic diseases [1] For these reasons, the term “functional food” is being used at an ever-increasing rate to indicate the antioxidant, anti-tumor or anti-inflammatory properties of many bioactive compounds extracted from plants or fruits [2,3,4]. Mango orchards are spread around the world, in both tropical and subtropical environments, finding suitable areas for cultivation in the Mediterranean area, where their spread first started in Spain, together with other tropical plants, colonized Sicily, at least 20 years ago [6,7,8] This fruit has received increasing interest from consumers who perceived its importance as a functional food rich in phytochemicals able to provide a healthy contribution to their diet. It has been observed that the peel and seed, usually discarded in fruit processing, are an important bio-source that can be exploited for their high content of polyphenols (mangiferin, quercetin, rhamnentin, ellagic acid and kaempferol), carotenoids, dietary fiber and vitamin E [9]
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