Aurone analog LYK01 exerts oxidative stress-dependent antiproliferation, G2/M arrest, apoptosis, and DNA damage of oral cancer cells involving MAPK modulation.

Aurones are plant flavonoids that generally exhibit oxidative stress and anticancer properties. We developed a novel aurone analog, LYK01, but its biological effects have yet to be examined, particularly in relation to its anticancer functions. In our experiment, LYK01 inhibited the proliferation of four types of oral cancer cells with limited cytotoxicity to normal oral cells, attenuated by N-acetylcysteine (NAC), demonstrating a selective ability to kill oral cancer cells. Regarding NAC pretreatment, the LYK01-induced mechanisms were confirmed to be oxidative stress-dependent. Mechanistically, LYK01 triggers G2/M arrest, oxidative stress (ROS and MitoSOX), DNA damage (γH2AX), and extrinsic caspase 8/3-based apoptosis to a greater extent in oral cancer cells than normal cells. Regarding MAPK inhibitors for p38, JNK, and ERK, LYK01-induced antiproliferation and apoptosis in oral cancer cells were attenuated. In conclusion, LYK01 exhibits preferential antiproliferative effects in oral cancer cells -mediated by oxidative stress and MAPK-associated pathways-while exhibiting limited cytotoxicity toward normal cells. These findings warrant in vivo and translational validation.