Department of Biochemical Science "A. Rossi Fanelli", Faculty of Pharmacy and Medicine, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
Enrico ed Enrica Sovena Foundation, 00199 Rome, Italy.
Molecules. 2021 Nov 25;26(23):7135. doi: 10.3390/molecules26237135.
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.
β-六氯环己烷（β-HCH）是一种在全球范围内广泛存在的污染物，它具有有机氯农药的所有理化特性，是多种非传染性疾病的环境风险因素。我们小组之前的体外研究揭示了β-HCH 的致癌潜力，它通过多种细胞内机制导致肿瘤转化。考虑到关于天然生物活性化合物对污染诱导毒性的保护作用的阳性证据，我们测试了具有调节β-HCH 细胞靶标能力的橄榄和番茄中的微量营养素。为此，对一种专利食品补充剂（No. EP2851080A1）获得的溶液（称为番茄和橄榄生物活性化合物（TOBC））进行了给药，并用不同的生化和细胞检测来评估其效率。TOBC 显示出剂量依赖性的显著化学保护作用，可对抗β-HCH 诱导的细胞内反应，如 STAT3 和 AhR 激活、AR 信号转导中断、抗凋亡和增殖活性以及 ROS 产生和 DNA 损伤增加。这些实验结果表明，TOBC 是一种合适的功能性食品，可以纳入旨在保护细胞免受β-HCH 负面影响的饮食方案中，并建议为暴露个体开发定制的富化配方。
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