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-α, 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-α pathway and ROS accumulation. Lung cancer is one of the most common cancers in the world. More than 2.0 million new cases are diagnosed each year. The World Health Organization (WHO) divides lung cancer into non-small-cell lung carcinoma (NSCLC) and small-cell lung carcinoma (SCLC). NSCLC accounts for 80-85% of all lung cancer cases, is characterized by high recurrence rate and drug resistance, and its 5-year survival rate is about 15-20% (1-4). This underlines the need to develop effective drugs for treatment and overcome the clinical challenges involved in NSCLC (5). Necrosis is an acute form of cell death triggered by unexpected injuries (6, 7), which destroy cell structure. When apoptosis fails to occur, cells die by necrosis (8). Necrosis is divided into non-programmed necrosis (or simply necrosis) and programmed necrosis (or necroptosis), depending on whether it is initiated by the activation of a specific receptor or sensor on the cell surface or inside the cell to induce a multi-step signal transduction, as well as a variety of molecular biological reactions (9). Several receptor-mediated signal transduction pathways are involved in necroptosis. For example, binding of tumor necrosis factor-α (TNF-α) to TNFR induces programmed cell death pathway. TNFR-associated death domain (TRADD) is associated with the receptor-interacting protein kinase 1 (RIP1), cellular apoptosis inhibitor 1/2 (cIAP1/2) and TNFR-1193 This article is freely accessible online.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.