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Voriconazole and Development of Squamous Cell Carcinoma: Potential Mechanism Identified

By: Hillary Ojeda
Posted: Tuesday, November 26, 2019

Prolonged use of the antifungal medication voriconazole seems to cause oxidative stress in skin cells, thus promoting ultraviolet-induced DNA damage, which may lead to the development of aggressive squamous cell carcinoma, according to a study published in Experimental Dermatology. However, the common antioxidant acetylcysteine may prove to mitigate the cancer-inducing effects of voriconazole in keratinocytes. John T. Seykora, MD, PhD, of the University of Pennsylvania, and colleagues emphasized the need for human trials to further understand this biologic mechanism and how best to prevent it.

“Conducting human trials to show that the combination of voriconazole and N-acetylcysteine is safe and effective is the next step in this research,” stated Dr. Seykora in a Penn Medicine press release. “Since N-acetylcysteine has existed for years and is a common treatment for other conditions, we anticipate a safe pairing.”

By analyzing several assays, a genetic mouse model, and human keratinocytes, the authors assessed the impact of voriconazole. Cells were exposed to the vehicle alone or 25 μM of either voriconazole or fluconazole for up to 6 days. Keratinocytes that received 25 μM of voriconazole with and without ultraviolet (UV) rays showed diminished cell growth 5 days after UV exposure. Additionally, voriconazole and voriconazole plus UV inhibited keratinocyte growth; however, inhibition was higher with voriconazole plus UV at day 3.

“In this study, we present novel data showing that the parent compound voriconazole has direct effects on human and murine keratinocytes that are procarcinogenic in the UV setting,” the authors commented.

Then, the team went on to pretreat human skin cells in culture with N-acetylcysteine to help mitigate the effects of increased oxidative stress. They found that the antioxidant reduced two markers of oxidative stress in mouse skin tissue exposed to UV radiation.

Disclosure: The study authors reported no conflicts of interest.



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