Differential sensitivities of HeLa and MCF-7 cells at G1-, S-, G2-and M-phase of the cell cycle to cold atmospheric plasma

Cold atmospheric plasma (CAP) is a novel modality for cancer therapy with high selectivity, and few side effects without the chance of drug resistance. However, fully determining the cellular targets of CAP and improving the clinical applicability of CAP remain challenging. Here, we assessed the sensitivity of cancer cells in different phases of the cell cycle to plasma to find the 'sensitive period' in cancer cells to plasma. Plasma was shown to exert significant anticancer effects on HeLa and MCF-7 cells at different phases during the cell cycle. The anticancer effects of plasma are irradiation time- and incubation time-dependent. However, although plasma-induced extracellular and intracellular oxidative pressure are identical, throughout the cell cycle, S- and M-phase cancer cells are more susceptible to plasma irradiation than G(1)- and G(2)-phase cells. Our results suggest that plasma induces the apoptosis of S-phase cancer cells by interfering with DNA replication and M-phase cells by impeding sister chromosome segregation. Therefore, the anti-cancer efficiency of CAP techniques might be further improved by their combination with an anticarcinogen that blocks the cell cycle in the 'sensitive period'.