Differential Cell Death In Hepatocellular Cell Lines Induced By Non-Thermal Plasma

Cancer recurrence, which is frequently accompanied by chemotherapy, has been a challenge in cancer treatment. Non-thermal plasma (NTP) has been recognized as a promising tool across a vast variety of biomedical applications including as a potential new therapeutic modality for cancer, with the potential of creating novel therapeutic methods. However, its mechanism of action remains unclear. In this study we examined the influence of non-thermal air-plasma on human hepatocellular carcinoma cell lines. We show how air non-thermal plasma induces cell death in two hepatocellular carcinoma cell lines (HepG2 and Huh7) via the formation of multiple intracellular reactive oxygen/nitrogen species. Interestingly, NTP demonstrated greater selective anti-proliferative activity against Huh7 cells relative to HepG2. Our results showed a discrepancy in the superoxide accumulation and lysosomal activity in response to plasma in these cell lines, suggesting that plasma-triggered signaling cascades might be grossly different between HepG2 and Huh7. Additionally, NTP induced distinct reactive oxygen species compartmentalization in two different hepatocellular carcinoma cell lines. In Huh7 plasma treatment resulted in nuclear accumulation of superoxide, whereas in HepG2 superoxide was diffusively distributed in cytosol. Our findings offer novel insight into plasma-induced cellular responses, and provide a basis for better controlled biomedical applications.