2. Academic Validation
  3. STAT3 Pathways Contribute to β-HCH Interference with Anticancer Tyrosine Kinase Inhibitors

STAT3 Pathways Contribute to β-HCH Interference with Anticancer Tyrosine Kinase Inhibitors

  • Int J Mol Sci. 2024 Jun 4;25(11):6181. doi: 10.3390/ijms25116181.
Sara Fiorini 1,  Elisabetta Rubini 2,  Monia Perugini 3,  Fabio Altieri 1,  Silvia Chichiarelli 1,  Giorgia Meschiari 1,  Giulia Arrighetti 4,  John Vijgen 5,  Pier Giorgio Natali 6 7,  Marco Minacori 1 3,  Margherita Eufemi 1
Affiliations

Affiliations

  • 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.
  • 2 Institute of Molecular Biology and Pathology, CNR National Research Council, Via degli Apuli, 4, 00185 Rome, Italy.
  • 3 Department of Bioscience and Agro-Food and Environmental Technology, University of Teramo, Campus "Aurelio Saliceti", Via R. Balzarini 1, 64100 Teramo, Italy.
  • 4 Department of Cultures, Politics and Society, University of Turin, Via Verdi, 8, 10124 Turin, Italy.
  • 5 International HCH and Pesticides Association (IHPA), Elmevej 14, 2840 Holte, Denmark.
  • 6 Collegium Ramazzini, Castello di Bentivoglio, Via Saliceto, 3, 40010 Bologna, Italy.
  • 7 Lega Italiana per la Lotta contro i Tumori (LILT), Associazione Metropolitana di Roma, Via Nomentana, 303, 00162 Rome, Italy.
PMID: 38892372 DOI: 10.3390/ijms25116181
Abstract

Organochlorine pesticides (OCPs) are a class of environmentally persistent and bioaccumulative pollutants. Among these, β-hexachlorocyclohexane (β-HCH) is a byproduct of lindane synthesis, one of the most worldwide widespread pesticides. β-HCH cellular mechanisms inducing chemical carcinogenesis correspond to many of those inducing chemoresistance, in particular, by the activation of signal transducer and activator of transcription 3 (STAT3) signaling pathways. For this purpose, four cell lines, representative of breast, lung, prostate, and hepatocellular cancers, were treated with β-HCH, specific tyrosine kinase inhibitors (TKIs), and a STAT3 Inhibitor. All cell samples were analyzed by a viability assay, immunoblotting analysis, a wound-healing assay, and a colony formation assay. The results show that β-HCH reduces the efficacy of TKIs. The STAT3 protein, in this context, plays a central role. In fact, by inhibiting its activity, the efficacy of the Anticancer drug is restored. Furthermore, this manuscript aimed to draw the attention of the scientific and socio-healthcare community to the issue of prolonged exposure to contaminants and their impact on drug efficacy.

Keywords

STAT3; chemoresistance; environmental pollutants; signaling transduction; β-hexachlorocyclohexane.

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