Abstract
Cutaneous squamous cell carcinoma (SCC) is the most prevalent cancer worldwide, increasing the cost of healthcare services and with a high rate of morbidity. Its etiology is linked to chronic ultraviolet (UV) exposure that leads to malignant transformation of keratinocytes. Invasive growth and metastasis are severe consequences of this process. Therapy-resistant and highly aggressive SCC is frequently fatal, exemplifying the need for novel treatment strategies. Cold physical plasma is a partially ionized gas, expelling therapeutic doses of reactive oxygen and nitrogen species that were investigated for their anticancer capacity against SCC in vitro and SCC-like lesions in vivo. Using the kINPen argon plasma jet, a selective growth-reducing action of plasma treatment was identified in two SCC cell lines in 2D and 3D cultures. In vivo, plasma treatment limited the progression of UVB-induced SSC-like skin lesions and dermal degeneration without compromising lesional or non-lesional skin. In lesional tissue, this was associated with a decrease in cell proliferation and the antioxidant transcription factor Nrf2 following plasma treatment, while catalase expression was increased. Analysis of skin adjacent to the lesions and determination of global antioxidant parameters confirmed the local but not systemic action of the plasma anticancer therapy in vivo.
Highlights
Non-melanocytic skin cancer (NMSC) is one of the most frequently diagnosed types of cancer [1].It includes, for instance, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), which representCancers 2020, 12, 1993; doi:10.3390/cancers12071993 www.mdpi.com/journal/cancersCancers 2020, 12, 1993 up to 20% of all skin cancers [2]
Since plasma treatment generates a plethora of reactive oxygen and nitrogen species simultaneously, which subsequently act on the skin, it was natural to investigate parameters of the antioxidant defense
nuclear factor E2-related factor 2 (Nrf2) levels were markedly elevated in UVB-treated skin compared to non-irradiated skin, indicating a putative involvement of Nrf2 in the pathology of SCC
Summary
Non-melanocytic skin cancer (NMSC) is one of the most frequently diagnosed types of cancer [1].It includes, for instance, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), which representCancers 2020, 12, 1993; doi:10.3390/cancers12071993 www.mdpi.com/journal/cancersCancers 2020, 12, 1993 up to 20% of all skin cancers [2]. Non-melanocytic skin cancer (NMSC) is one of the most frequently diagnosed types of cancer [1]. It includes, for instance, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), which represent. Recent work using genetic mouse models of BCC described that stem and progenitor cells are the probable sources of BCC initiation [3]. This type of NMSC can be locally destructive, but metastasis is rare [4]. SCC is more aggressive and characterized by an uncontrolled proliferation of squamous cells in the epidermal layer. SCCs often contain squamous pearls, a keratinized structure, wherein abnormal squamous cells form concentric layers and occasionally mitotic figures [5]
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