Temozolomide-perillyl alcohol conjugate induced reactive oxygen species accumulation contributes to its cytotoxicity against non-small cell lung cancer

Temozolomide-perillyl alcohol conjugate (TMZ − POH), a novel temozolomide analog, was reported to play a cytotoxic role in triple-negative breast cancer and TMZ-resistant gliomas. In a current study we had demonstrated how TMZ − POH also exhibited its cytotoxicity against non-small cell lung cancer (NSCLC), the most common type of lung cancer, as evidence from cell/tumor proliferation inhibition, G2/M arrest, DNA damage and mitochondrial apoptosis. Importantly, TMZ − POH’s cytotoxicity is closely related to reactive oxygen species (ROS) accumulation because it can be reversed by two ROS scavengers, catalase (CAT) and N-acetyl-L-cysteine (NAC). TMZ − POH induces mitochondrial transmembrane potential (MTP) decrease and ROS accumulation, in turn activates mitogen-activated protein kinase (MAPKs) signaling and mitochondrial apoptosis, and then exerts its cytotoxicity, thus proposing TMZ − POH as a potential therapeutic candidate for NSCLC.