Oxaliplatin induces the PARP1-mediated parthanatos in oral squamous cell carcinoma by increasing production of ROS
Dongfang Li, Yuying Kou, Yuan Gao, Shanshan Liu, Panpan Yang, Tomoka Hasegawa, Rongjian Su, Jie Guo, Minqi Li
Abstract
. Further experiments proved that oxaliplatin induced parthanatos in OSCC cells, characterized by depolarization of the mitochondrial membrane potential, up-regulation of PARP1, AIF and MIF in the nucleus, as well as the nuclear translocation of AIF. Meanwhile, PARP1 inhibitor rucaparib and siRNA against PARP1 attenuated oxaliplatin-induced parthanatos in OSCC cells. In addition, we found that oxaliplatin caused oxidative stress in OSCC cells, and antioxidant NAC not only relieved oxaliplatin-induced overproduction of reactive oxygen species (ROS) but also reversed parthanatos caused by oxaliplatin. In conclusion, our results indicate that oxaliplatin inhibits OSCC by activating PARP1-mediated parthanatos through increasing the production of ROS.