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Tomato and Olive Bioactive Compounds: A Natural Shield against the Cellular Effects Induced by β-Hexachlorocyclohexane-Activated Signaling Pathways
Authors:Elisabetta Rubini  Marco Minacori  Giuliano Paglia  Alberto Macone  Silvia Chichiarelli  Fabio Altieri  Margherita Eufemi
Affiliation:1.Department of Biochemical Science “A. Rossi Fanelli”, Faculty of Pharmacy and Medicine, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (E.R.); (M.M.); (G.P.); (A.M.); (S.C.); (M.E.);2.Enrico ed Enrica Sovena Foundation, 00199 Rome, Italy;3.Fondazione Federico Calabresi Onlus, 00186 Rome, Italy
Abstract:The β-isomer of hexachlorocyclohexane (β-HCH) is a globally widespread pollutant that embodies all the physicochemical characteristics of organochlorine pesticides, constituting an environmental risk factor for a wide range of noncommunicable diseases. Previous in vitro studies from our group disclosed the carcinogenic potential of β-HCH, which contributes to neoplastic transformation by means of multifaceted intracellular mechanisms. Considering the positive evidence regarding the protective role of natural bioactive compounds against pollution-induced toxicity, micronutrients from olive and tomato endowed with the capability of modulating β-HCH cellular targets were tested. For this purpose, the solution obtained from a patented food supplement (No. EP2851080A1), referred to as Tomato and Olive Bioactive Compounds (TOBC), was administered to the androgen-sensitive prostate cancer cells LNCaP and different biochemical and cellular assays were performed to evaluate its efficiency. TOBC shows a dose-dependent significant chemoprotection by contrasting β-HCH-induced intracellular responses such as STAT3 and AhR activation, disruption of AR signaling, antiapoptotic and proliferative activity, and increase in ROS production and DNA damage. These experimental outcomes identified TOBC as a suitable functional food to be included in a diet regimen aimed at defending cells from β-HCH negative effects, recommending the development of tailored enriched formulations for exposed individuals.
Keywords:environmental disease, cancer, environmental pollution, organochlorine pesticides, β  -hexachlorocyclohexane, natural dietary compounds, signaling pathways
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