STAT3, a Hub Protein of Cellular Signaling Pathways, Is Triggered by ß-Hexaclorocyclohexane.

ABSTRACT

BACKGROUND: Organochlorine pesticides (OCPs) are widely distributed in the environment and their toxicity is mostly associated with the molecular mechanisms of endocrine disruption. Among OCPs, particular attention was focused on the effects of ß-hexaclorocyclohexane (ß-HCH), a widely common pollutant. A detailed epidemiological study carried out on exposed population in the "Valle del Sacco" found correlations between the incidence of a wide range of diseases and the occurrence of ß-HCH contamination. Taking into account the pleiotropic role of the protein signal transducer and activator of transcription 3 (STAT3), its function as a hub protein in cellular signaling pathways triggered by ß-HCH was investigated in different cell lines corresponding to tissues that are especially vulnerable to damage by environmental pollutants. MATERIALS AND METHODS: Human prostate cancer (LNCaP), human breast cancer (MCF-7 and MDA-MB 468), and human hepatoma (HepG2) cell lines were treated with 10 µM ß-HCH in the presence or absence of specific inhibitors for different receptors. All samples were subjected to analysis by immunoblotting and RT-qPCR. RESULTS AND CONCLUSIONS: The preliminary results allow us to hypothesize the involvement of STAT3, through both its canonical and non-canonical pathways, in response to ß-HCH. Moreover, we ascertained the role of STAT3 as a master regulator of energy metabolism via the altered expression and localization of HIF-1α and PKM2, respectively, resulting in a Warburg-like effect.