1. Academic Validation
  2. Citronellol Induces Necroptosis of Human Lung Cancer Cells via TNF-α Pathway and Reactive Oxygen Species Accumulation

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

  • In Vivo. 2019 Jul-Aug;33(4):1193-1201. doi: 10.21873/invivo.11590.
Wan-Nien Yu 1 Ying-Ju Lai 2 3 Jui-Wen Ma 4 Chi-Tang Ho 5 Shan-Wei Hung 4 Yu-Hsin Chen 6 Chiung-Tong Chen 2 3 7 Jung-Yie Kao 8 Tzong-DER Way 8 7 9
Affiliations

Affiliations

  • 1 Department of Otolaryngology, Head and Neck Surgery, Changhwa Christian Hospital, Changhwa, Taiwan, R.O.C.
  • 2 Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
  • 3 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan, R.O.C.
  • 4 Institute of Biochemistry, College of Life Science, National Chung Hsing University, Taichung, Taiwan, R.O.C.
  • 5 Department of Food Science, Rutgers University, New Brunswick, NJ, U.S.A.
  • 6 Taichung District Agricultural Research and Extension Station, Council of Agriculture, Taichung, Taiwan, R.O.C.
  • 7 Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan, R.O.C.
  • 8 Institute of Biochemistry, College of Life Science, National Chung Hsing University, Taichung, Taiwan, R.O.C. tdway@mail.cmu.edu.tw biosjky@gmail.com.
  • 9 Department of Health and Nutrition Biotechnology, College of Health Science, Asia University, Taichung, Taiwan, R.O.C.
Abstract

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.

Keywords

Citronellol; essential oil of Pelargonium capitatum (EOPC); necroptosis; non-small-cell lung cancer (NSCLC); reactive oxygen species (ROS).

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