Plasma as adjuvant in melanoma treatment via mitochondrial targeting

Abstract

Cutaneous melanoma is a highly aggressive malignancy and has rapidly increased over the past several decades [1]. Although the clinical biology and pathogenesis of melanoma are well understood, the prognosis remains poor with limited therapeutic options in the metastatic stage of the disease [2]. Reactive oxygen species (ROS) may be drivers of carcinogenesis and may cause oxidative damage to several cellular components, so it is generally considered to be deleterious [3]. However, ROS, as well as the products generated during redox reactions can act as second messengers and participates of signaling pathways, activating redox-sensitive transcription factors and gene expressions leading to cell proliferation, metastasis, and therapy resistance [4]. Although antioxidants can prevent the onset of melanoma [5], studies have shown that a systemic pro oxidant status is necessary to prevent distant metastases [6]. Consequently, some therapies aim at the generation of ROS as a mechanism of death [7]. Despite advances in chemotherapy, immunotherapy, and radiotherapy, the success in drug treatment of disseminated disease remains limited. The large number of side effects and resistance to treatment are the main causes of unsuccessful therapy. Thus, it is necessary to search for new strategies that can increase patient survival and quality of life. Cold plasma is a partially ionized gas proved its effectiveness for different applications in health care and medicine. It has been shown to exert various biologic effects to living tissue and cells ranging from cytoprotective to cytotoxic potency depending on the applied technique [8]. The gas generates reactive oxygen and nitrogen species [9] that are being deposited in cell culture media [10]. Such oxidant-enriched media selectively kills cancer cells in vitro by targeting the mitochondrial network [11], but the exact mechanism is still unclear. We aim at therapeutic strategies combining chemotherapy/radiotherapy with cold plasma as a strategy against melanoma. In addition, we studied the mitochondrial action mechanism of plasma, elucidating its possible target.