Cold Atmospheric Plasma-Activated Media Improve Paclitaxel Efficacy on Breast Cancer Cells in a Combined Treatment Model

Abstract

The use of plasma-activated media (PAM), an alternative to direct delivery of cold atmospheric plasma to cancer cells, has recently gained interest in the plasma medicine field. Paclitaxel (PTX) is used as a chemotherapy of choice for various types of breast cancers, which is the leading cause of mortality in females due to cancer. In this study, we evaluated an alternative way to improve anti-cancerous efficiency of PTX by association with PAM, the ultimate achievement being a better outcome in killing tumoral cells at smaller doses of PTX. MCF-7 and MDA-MB-231 cell lines were used, and the outcome was measured by cell viability (MTT assay), the survival rate (clonogenic assay), apoptosis occurrence, and genotoxicity (COMET assay). Treatment consisted of the use of PAM in combination with under IC50 doses of PTX in short- and long-term models. The experimental data showed that PAM had the capacity to improve PTX’s cytotoxicity, as viability of the breast cancer cells dropped, an effect maintained in long-term experiments. A higher frequency of apoptotic, dead cells, and DNA fragmentation was registered in cells treated with the combined treatment as compared with those treated only with PT. Overall, PAM had the capacity to amplify the anti-cancerous effect of PTX.

Efficacy of Cold Atmospheric Plasma vs. Chemotherapy in Triple-Negative Breast Cancer: A Systematic Review

“…Interestingly, CAP treatment and chemotherapy drugs, specifically paclitaxel and olaparib, were combined in two studies [ 19 , 51 ]. Olaparib showed a tendency to improve the efficacy of CAP in all cell lines [ 51 ].…”

“…Moreover, the chemosensitivity to paclitaxel (0.01 µM) was improved after 15 seconds of CAP exposure. According to clonogenic assay, the combined treatment decreased the number of colonies to a number similar to or even smaller than that specific to PAM or paclitaxel [ 19 ].…”

“…Here, we examine two different strategies concerning the application of CAP in TNBC cell lines, namely CAP and PAM, which used different exposure times and solutions. Both strategies are also reported in preclinical studies regarding other types of cancer [ 17 , 18 , 19 , 44 , 99 , 100 , 101 ]. Different types of equipment that are able to generate CAP are described.…”

“…Some authors used a flow of gases such as argon or helium [ 34 , 44 , 53 , 62 , 77 ], and the frequency and high voltage were also dependent on the equipment of each research group. Generally, the exposure times were 60 seconds or 120 seconds [ 19 , 20 , 21 , 33 , 35 , 44 , 51 , 52 , 53 , 55 , 71 , 80 , 81 ]. The reduction of cell viability in TNBC cells was time dependent in all studies.…”

“…Several methods for producing it have been described [ 15 ]. CAP has recently been studied as a potential cancer treatment, with evidence obtained in several malign neoplasms both in vitro and in vivo [ 16 , 17 , 18 , 19 , 20 ]. Some authors have demonstrated CAP selectivity to tumoral cells compared to non-malignant counterparts, highlighting its potential in cancer treatment [ 21 , 22 , 23 ].…”