Effect of plasma activated media, with and without chemotherapeutics, on viability of normal and malignant human breast cells

Chemotherapy used for cancer treatment results in debilitating side effects for patients. Despite decades of research, enhancing drug sensitivity and minimizing toxicity remains a major challenge. Cold atmospheric plasma (CAP) offers a novel, non-thermal strategy to address this gap. CAP can alter biological processes at the cellular levelto amplify the effects of existing chemotherapeutics. However, the comparative impact of plasma-treated media on normal tissues remains poorly understood and represents a critical barrier to clinical translation. Therefore, the goal wasto determine the effect of the plasma-treated media, alone or in combination with chemotherapeutics, on viability of normal and malignant human breast cells. We conducted a series of experiments using malignant breast MCF-7 and MDA-MB-231 cell lines, and the corresponding normal breast MCF-10A cell line to assess the effects of plasma-treated media combined with different chemotherapeutic agents; paclitaxel, docetaxel, doxorubicin, cisplatin, carboplatin, 5-fluorouracil, and gemcitabine. Media were exposed to dielectric barrier discharge (DBD) air plasma for 5, 10, or 20 minutes before drug administration. Our results demonstrated that breast cancer cell lines showed limited responsiveness to plasma-treated media, whereas normal cells were markedly susceptible. Neither MCF-7 nor MDA-MB-231 cells displayed significant changes in viability following 5-minute plasma exposure, and only modest reductions were observed at 10- and 20-minute exposures across most drug conditions. Among the chemotherapeutics tested, docetaxel at 1 μM exhibited the most pronounced plasma-enhanced reduction in cancer cell viability. In contrast, MCF-10A cells demonstrated heightened sensitivity to plasma-treated media, consistently exhibiting approximately twice the loss of viability observed in cancer cells across nearly all treatment groups. These findings suggest that, within the current DBD air-plasma setup, the oxidative burden generated is disproportionately harmful to normal epithelial breast cell lines and does not produce a correspondingly advantageous cytotoxic effect in the malignant breast cell lines tested. Future studies will evaluate the effect of different types of plasma, alone or combined with chemotherapeutics, on both normal and breast cancer cells, and will investigate the underlying mechanisms.