Cold Atmospheric Plasma Potentiates the Anticancer Activity of L-Ascorbic Acid, Curcumin, and Salinomycin in Human Breast Cancer Cell Lines.

Abstract

Cold atmospheric plasma (CAP) has emerged as a promising strategy for cancer therapy due to its ability to generate reactive oxygen and nitrogen species (RONS) capable of modulating cellular redox homeostasis. In the present study, two helium atmospheric pressure plasma jet (APPJ) configurations, including surface and subcutaneous delivery modules, were investigated for their ability to sensitize breast cancer cell lines to selected anti-cancer compounds, namely L-ascorbic acid, curcumin, and salinomycin. Optical emission spectroscopy confirmed the generation of multiple short-lived RONS. The subcutaneous APPJ configuration exhibited enhanced oxidative potential, as well as elevated concentrations of H2O2, NO2-, and H2O2-equivalent oxidizing capacity. Scavenging experiments revealed distinct scavenger-sensitive oxidizing pathways in the two APPJ configurations, with a greater contribution of pyruvate-sensitive chemistry in subcutaneous APPJ. Biological investigations performed on MCF10A, MCF7, and MDA-MB-231 cell lines indicated that both CAP treatment and the investigated anti-cancer compounds induced biological responses. Moreover, CAP treatment elicited clear effects across the studied models, whereas a consistent additive effect was observed in the combined CAP treatments in the MCF7 cell line. The most pronounced responses were observed for the subcutaneous APPJ configuration, particularly in tumor cell lines, including reduced proliferation and migration, increased apoptotic signaling, and modulation of oxidative stress markers. The obtained results demonstrate that mode of CAP delivery significantly influences plasma-liquid interactions, RONS transfer, and the resulting biological response. Overall, the presented findings indicate that CAP may represent a useful component in combinatory anti-cancer strategies and suggest that further optimization of operational parameters could contribute to the development of plasma-assisted cancer treatment approaches.

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