Pleiotropic Devitalization of Renal Cancer Cells by Non-Invasive Physical Plasma: Characterization of Molecular and Cellular Efficacy.

Simple Summary: Renal cell carcinoma (RCC) has an extremely poor prognosis, as there are few therapeutic options. In addition, resistance often develops during the administration of cytostatic drugs, preventing further drug-based therapy. New therapeutic modalities to reduce tumor cells would therefore be an important advance in the cancer therapy of RCC. In the present research study, non-invasive physical plasma (NIPP) was used to treat RCC cells. It was found that both cell growth and cell motility of RCC cells could be significantly reduced. Furthermore, programmed cell death was induced, so that some of the cancer cells actually died. Cellular analysis of NIPP treated cancer cells indicated that exposure to NIPP resulted in increased permeability of the cytoplasmic membrane to low molecular weight substances. This may contribute to the inhibition of the physiological activities of the cancer cells. The present results suggest that treatment with NIPP may represent a promising, innovative, and non-chemical option for the therapy of RCC and cancer in general. In combination with established therapeutic modalities, therapeutic effects would be enhanced and resistance would be minimized by the simultaneous application of multiple modes of action. Renal cell carcinoma (RCC) is the third most common urological tumor and has an extremely poor prognosis after metastasis has occurred. Therapeutic options are highly restricted, primarily due to resistance to classical chemotherapeutics. The development of new, innovative therapeutic procedures is thus of great urgency. In the present study, the influence of non-invasive physical plasma (NIPP) on malignant and non-malignant renal cells is characterized. The biological efficacy of NIPP has been demonstrated in malignant renal cell lines (786-O, Caki-1) and non-malignant primary human renal epithelial cells (HREpC). The cell responses that were experimentally examined were cell growth (cell number determination, calculation of growth rate and doubling time), cell motility (scratch assay, invasiveness assay), membrane integrity (uptake of fluorescent dye, ATP release), and induction of apoptosis (TUNEL assay, caspase-3/7 assay, comet assay). A single NIPP treatment of the malignant cells significantly inhibited cell proliferation, invasiveness, and metastasis. This treatment has been attributed to the disruption of membrane functionality and the induction of apoptotic mechanisms. Comparison of NIPP sensitivity of malignant 786-O and Caki-1 cells with non-malignant HREpC cells showed significant differences. Our results suggest that renal cancer cells are significantly more sensitive to NIPP than non-malignant renal cells. Treatment with NIPP could represent a promising innovative option for the therapy of RCC and might supplement established treatment procedures. Of high clinical relevance would be the chemo-sensitizing properties of NIPP, which could potentially allow a combination of NIPP treatment with low-dose chemotherapy. [ABSTRACT FROM AUTHOR]