Tomato and Olive Bioactive Compounds: A Natural Shield against the Cellular Effects Induced by β-Hexachlorocyclohexane-Activated Signaling Pathways

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.

Development of the whole tomato and olive-based food supplement enriched with anti-platelet aggregating nutrients

“…A possible unifying mechanism underlining the antiplatelet activities of carotenoids and polyphenols involving signal transducer and activator of transcription 3 (STAT3) signaling can be hypothesized. Indeed, several phenolic components of WTBFS can inhibit STAT3 activation in a dose-dependent manner (Table 2; Rubini et al, 2021). As a signaling molecule and transcription factor, STAT3 plays a key role in megakaryocyte development and platelet production and function.…”

“…The lipophilic solution of WTBFS (Lycoprozen, kindly provided Janus Pharma srl, Roma) was obtained and characterized as recently detailed (Rubini et al, 2021). Briefly, 1 g of WTBFS was added to 10 mL of the organic solvent dimethyl sulfoxide (DMSO) to make available to cells as much active molecules as possible.…”

Improving Whole Tomato Transformation for Prostate Health: Benign Prostate Hypertrophy as an Exploratory Model

“…Although numerous plant compounds have revealed bioactive properties, including antioxidant, anti-inflammatory, and anticancer, the combination of the tomato and the olive has several advantages: (a) none of the other “plant compounds” have the properties of tomato and olive in terms of fulfilling the criteria that we have referred to in the section “Tomato and olive eco sustainability” [ 13 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ], representing a limitation in their use as functional foods; (b) a dose-dependent effect has been demonstrated only for a limited number of plants; (c) none of the other plant compounds are known to concentrate in the prostate and to provide the complex of molecules with converging biological effects such as those summarized in Table 1 ; and (d) when dealing with aging-related prostate diseases, the WTBS is also endowed with anti-androgen receptor inhibition [ 120 ].…”

“…Furthermore, recent data created using the androgen-sensitive human prostate epithelial cell line LNCaP exposed to an environmental carcinogen have demonstrated that WTFS protects DNA from oxidative stress damage, blocks the pathways involved in PCa development—such as STAT3 activation androgen receptor signaling—and displays pro-apoptotic and anti-proliferative properties [ 120 ]. Table 1 summarizes the biological activities of the complex of micronutrients present in the WTFS.…”