Persistent β-Hexachlorocyclohexane Exposure Impacts Cellular Metabolism with a Specific Signature in Normal Human Melanocytes

Autor: Federica Papaccio, Silvia Caputo, Alessandra Iorio, Paola De Simone, Monica Ottaviani, Antonella Del Brocco, Pasquale Frascione, Barbara Bellei
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cells, Vol 13, Iss 5, p 374 (2024)
Druh dokumentu: article
ISSN: 2073-4409
26447533
DOI: 10.3390/cells13050374
Popis: Background: Cutaneous melanoma arises from skin melanocytes and has a high risk of metastatic spread. Despite better prevention, earlier detection, and the development of innovative therapies, melanoma incidence and mortality increase annually. Major clinical risk factors for melanoma include fair skin, an increased number of nevi, the presence of dysplastic nevi, and a family history of melanoma. However, several external inducers seem to be associated with melanoma susceptibility such as environmental exposure, primarily unprotected sun experience, alcohol consumption, and heavy metals. In recent years, epidemiological studies have highlighted a potential risk of β-hexachlorocyclohexane (β-HCH), the most studied organochlorine pesticide, causing cancer induction including melanoma. Methods: We evaluated in vitro the impact of this pollutant on epidermal and dermal cells, attempting to describe mechanisms that could render cutaneous cells more prone to oncogenic transformation. Results: We demonstrated that β-HCH impacts melanocyte biology with a highly cell-type specific signature that involves perturbation of AKT/mTOR and Wnt/β-catenin signaling, and AMPK activation, resulting in lowering energy reserve, cell proliferation, and pigment production. Conclusions: In conclusion, long-term exposure to persistent organic pollutants damages melanocyte metabolism in its function of melanin production with a consequent reduction of melanogenesis indicating a potential augmented skin cancer risk.
Databáze: Directory of Open Access Journals
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