Non-thermal atmospheric pressure plasma induces apoptosis in oral cavity squamous cell carcinoma: Involvement of DNA-damage-triggering sub-G(1) arrest via the ATM/p53 pathway.

Abstract

Recent advances in physics have made possible the use of non-thermal atmospheric

pressure plasma (NTP) in cancer research. Although increasing evidence suggests

that NTP induces death of various cancer cell types, thus offering a promising

alternative treatment, the mechanism of its therapeutic effect is little

understood. In this study, we report for the first time that NTP led to apoptotic

cell death in oral cavity squamous cell carcinoma (OSCC). Interestingly, NTP

induced a sub-G(1) arrest in p53 wild-type OSCCs, but not in p53-mutated OSCCs.

In addition, NTP increased the expression levels of ATM, p53 (Ser 15, 20 and 46),

p21, and cyclin D1. A comet assay, Western blotting and immunocytochemistry of

gammaH2AX suggested that NTP-induced apoptosis and sub-G(1) arrest were

associated with DNA damage and the ATM/p53 signaling pathway in SCC25 cells.

Moreover, ATM knockdown using siRNA attenuated the effect of NTP on cell death,

sub-G(1) arrest and related signals. Taken together, these results indicate that

NTP induced apoptotic cell death in p53 wild-type OSCCs through a novel mechanism

involving DNA damage and triggering of sub-G(1) arrest via the ATM/p53 pathway.

These findings show the therapeutic potential of NTP in OSCC.