Citronellol Induces Necroptosis of Human Lung Cancer Cells via TNF-α Pathway and Reactive Oxygen Species Accumulation

Background/Aim: Our current study aimed to determine the molecular mechanisms of citronellol-induced cell death and ROS accumulation in non-small cell lung cancer (NCI-H1299 cells) and also compare the anticancer effects of citronellol and EOPC. Materials and Methods: ROS measurement and western blotting were performed to detect whether citronellol can induce necroptosis in vitro. Besides, we performed an in vivo analysis of tumourigenesis inhibition by citronellol treatment in BALB/c (nu/nu) nude mice. Results: Necroptosis occured by up-regulating TNF-alpha, RIP1/RIP3 activities, and down-regulating caspase-3/caspase-8 activities after citronellol treatment in NCI-H1299 cells. Citronellol also resulted in a biphasic increase in ROS production at 1 h and at 12 h in NCI-H1299 cells. Xenograft model experiments showed that citronellol could effectively inhibit subcutaneous tumours produced 4 weeks after intraperitoneal injection of NCI-H1299 in BALB/c nude mice. Conclusion: Citronellol induced necroptosis of NCI-H1299 cells via TNF-alpha pathway and ROS accumulation.