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

Molecules. 2021 Nov 25;26(23):7135. doi: 10.3390/molecules26237135.

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: cancer; environmental disease; environmental pollution; natural dietary compounds; organochlorine pesticides; signaling pathways; β-hexachlorocyclohexane.

MeSH terms

  • Androgens / metabolism
  • Cell Proliferation / drug effects
  • DNA Damage / drug effects
  • Environmental Pollutants / toxicity
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hexachlorocyclohexane / toxicity
  • Humans
  • Male
  • Micronutrients / chemistry
  • Micronutrients / pharmacology
  • Olea / chemistry
  • Phytochemicals / chemistry
  • Phytochemicals / pharmacology*
  • Prostatic Neoplasms / chemically induced
  • Prostatic Neoplasms / diet therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Reactive Oxygen Species / chemistry
  • Receptors, Androgen / genetics*
  • Risk Factors
  • STAT3 Transcription Factor / genetics*
  • Signal Transduction / drug effects
  • Solanum lycopersicum / chemistry

Substances

  • AR protein, human
  • Androgens
  • Environmental Pollutants
  • Micronutrients
  • Phytochemicals
  • Reactive Oxygen Species
  • Receptors, Androgen
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Hexachlorocyclohexane