Cytotoxic and Antitumoral Effects of Methanolic Extracts of Avocado Fruit Mesocarp in Colorectal Cancer Cell Line HT29.

Abstract

Colorectal cancer is a widespread neoplasia with high ratios of chemoresistance. Phytochemicals in plant-based extracts could be useful to treat colorectal cancer, and/or reduce chemoresistance. Methanolic extract of avocado mesocarp (MEAM) has demonstrated antitumoral properties, depending on the fruit ripening stage (RS). The aim of this study was to analyze the effects of methanolic extracts of "Hass" avocado fruit at different RS on cytotoxicity, antioxidative, anti-inflammatory, anti-invasive, cell cycle, and epithelial-mesenchymal transition inhibition in colorectal adenocarcinoma cell line HT29. The MEAM showed an increasing concentration of total phenolic compounds as the RS progressed, which was correlated with antioxidant capacity measured by the Ferric Reducing Antioxidant Power assay but not with the 2.2-diphenyl-1-picrylhydrazyl assay. The specific phenolic compounds of MEAM were determined by high-performance liquid chromatography, and it was found that concentrations of epicatechin decreased while concentrations of chlorogenic acid increased as the RS progressed. The HT29 cell line was treated with MEAM for 48 h, and all MEAM had a cytotoxic effect, reported by MTT assay, nevertheless, the strongest effect was associated with the presence of chlorogenic acid. MEAM induced apoptosis and cell cycle arrest in phase G0/G1, reported by flow cytometry. Moreover, MEAM inhibited cell migration evidenced by the wound healing assay. On the other hand, MEAM significantly reduced expression of mRNA of tumor necrosis factor-alpha and cyclooxygenase 2. These effects comprise important inhibition of some hallmarks of cancer. This, in turn, may provide interesting guidelines for developing antitumoral intervention agents.