Differential roles of ATM and Chk2 in cold atmospheric helium plasma-induced cell death in Molt-4 human leukemia cell with intact or reduced p53 expression.

Cold atmospheric helium plasma (CAP) is a promising tool for cancer therapy. However, the mechanisms underlying CAP-induced DNA damage responses and cell death remains incompletely understood. Here, we investigated the role of the ATM-Chk2 pathway in CAP-induced cellular responses using a matched pair of p53-proficient (Molt-4/V) and p53-knockdown (Molt-4/shp53) cells. CAP exposure induced γH2AX/53BP1foci formation and activated ATM and Chk2 in both cell lines. CAP-induced cell death was more prominent in Molt-4/V cells, supporting a proapoptotic role of p53. In Molt-4/V cells, inhibition of ATM or Chk2 suppressed p53 accumulation and reduced CAP-induced cell death. In contrast, Chk2 inhibition modestly enhanced CAP-induced in Molt-4/shp53 cells cell death, suggesting a cytoprotective role for Chk2 in cells with reduced p53 expression. Hydrogen peroxide partially reproduced CAP-induced DNA damage response but with weaker effects, whereas nitrite had minimal impact under the condition tested. Collectively, these findings indicate that the ATM-Chk2 pathway contribute to CAP-induced cell death in a p53 dependent manner and suggest that its functional role differs according to p53 status, providing insight into how CAP-induced DNA damage response are modulated by p53 status.