Non-thermal plasma induces apoptosis accompanied by protective autophagy via activating JNK/Sestrin2 pathway

Although non-thermal plasma (NTP) has been proved to be an effective way to kill cancer cells, the mechanism of NTP-induced cancer cell death is still not clear. In this study, we found that NTP exposure caused reactive oxygen species generation and apoptosis in A549 and MDA-MB-231 cells. Meanwhile, NTP treatment also induced autophagy, as evidenced by the formation of acidic vesicular organelles and conversion of LC3-I to LC3-II. Suppression of autophagy by chloroquine significantly increased NTP-induced cell death, indicating that NTP-induced autophagy acted in a protective role from apoptosis. Furthermore, NTP treatment significantly increased Sestrin2 (Sesn2) expression and activated the JNK signaling pathway. Knocking down Sesn2 with special siRNA enhanced NTP-induced cell death, while pretreatment with JNK inhibitor abolished the increase of Sesn2 and LC3 formation, and promoted cell apoptosis induced by NTP. These indicated that the JNK/Sesn2 pathway was involved in autophagy and apoptosis induced by NTP. These findings provided evidence that supplement with autophagy inhibition might be a useful strategy to improve the tumor cell killing effect of NTP.