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Persistent β-Hexachlorocyclohexane Exposure Impacts Cellular Metabolism With a Specific Signature in the Human Normal Melanocytes: Implication in Melanomagenesis
Papaccio, F.; Caputo, S.; Iorio, A.; De Simone, P.; Ottaviani, M.; Del Brocco, A.; Frascione, P.; Bellei, B. Persistent β-Hexachlorocyclohexane Exposure Impacts Cellular Metabolism with a Specific Signature in Normal Human Melanocytes. Cells2024, 13, 374.
Papaccio, F.; Caputo, S.; Iorio, A.; De Simone, P.; Ottaviani, M.; Del Brocco, A.; Frascione, P.; Bellei, B. Persistent β-Hexachlorocyclohexane Exposure Impacts Cellular Metabolism with a Specific Signature in Normal Human Melanocytes. Cells 2024, 13, 374.
Papaccio, F.; Caputo, S.; Iorio, A.; De Simone, P.; Ottaviani, M.; Del Brocco, A.; Frascione, P.; Bellei, B. Persistent β-Hexachlorocyclohexane Exposure Impacts Cellular Metabolism with a Specific Signature in Normal Human Melanocytes. Cells2024, 13, 374.
Papaccio, F.; Caputo, S.; Iorio, A.; De Simone, P.; Ottaviani, M.; Del Brocco, A.; Frascione, P.; Bellei, B. Persistent β-Hexachlorocyclohexane Exposure Impacts Cellular Metabolism with a Specific Signature in Normal Human Melanocytes. Cells 2024, 13, 374.
Abstract
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, on 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 that converges in lowering energy reserve, cell proliferation, and pigment production. Conclusion: In conclusion, long-term exposure to persistent organic pollutants damages melanocyte metabolism in the function of the melanin content with a consequent reduction of melanogenesis indicating a potential augmented skin cancer risk.
Biology and Life Sciences, Biology and Biotechnology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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