1. Academic Validation
  2. Arnicolide D, from the herb Centipeda minima, Is a Therapeutic Candidate against Nasopharyngeal Carcinoma

Arnicolide D, from the herb Centipeda minima, Is a Therapeutic Candidate against Nasopharyngeal Carcinoma

  • Molecules. 2019 May 17;24(10):1908. doi: 10.3390/molecules24101908.
Rui Liu 1 Brandon Dow Chan 2 Daniel Kam-Wah Mok 3 4 Chi-Sing Lee 5 William Chi-Shing Tai 6 7 Sibao Chen 8 9 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen 518057, China. rayfayliuruifei@163.com.
  • 2 Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom 999077, Hong Kong, China. brandon.d.chan@connect.polyu.hk.
  • 3 State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen 518057, China. daniel.mok@polyu.edu.hk.
  • 4 Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom 999077, Hong Kong, China. daniel.mok@polyu.edu.hk.
  • 5 Department of Chemistry, The Hong Kong Baptist University, Kowloon Tong 999077, Hong Kong, China. cslee-chem@hkbu.edu.hk.
  • 6 State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen 518057, China. william-cs.tai@polyu.edu.hk.
  • 7 Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom 999077, Hong Kong, China. william-cs.tai@polyu.edu.hk.
  • 8 State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen 518057, China. sibao.chen@polyu.edu.hk.
  • 9 Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom 999077, Hong Kong, China. sibao.chen@polyu.edu.hk.
  • 10 Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. sibao.chen@polyu.edu.hk.
Abstract

Nasopharyngeal carcinoma (NPC) is a high morbidity and mortality Cancer with an obvious racial and geographic bias, particularly endemic to Southeast China. Our previous studies demonstrated that Centipeda minima extract (CME) exhibited anti-cancer effects in human NPC cell lines. Arnicolide C and arnicolide D are sesquiterpene lactones isolated from Centipeda minima. In this study, for the first time, we investigated their anti-NPC effects and further explored the related molecular mechanisms. The effects of both arnicolide C and arnicolide D were tested in NPC cells CNE-1, CNE-2, SUNE-1, HONE1, and C666-1. The results showed that the two compounds inhibited NPC cell viability in a concentration- and time-dependent manner. As the inhibitory effect of arnicolide D was the more pronounced of the two, our following studies focused on this compound. Arnicolide D could induce cell cycle arrest at G2/M, and induce cell Apoptosis. The molecular mechanism of cell cycle regulation and Apoptosis induction was investigated, and the results showed that arnicolide D could downregulate cyclin D3, cdc2, p-PI3K, p-AKT, p-mTOR, and p-STAT3, and upregulate cleaved PARP, cleaved Caspase 9, and Bax. Regulation of cyclin B1, CDK6, and Bcl-2 expression by arnicolide D showed dynamic changes according to dose and time. Taken together, arnicolide D modulated the cell cycle, activated the Caspase signaling pathway, and inhibited the PI3K/Akt/mTOR and STAT3 signaling pathways. These findings provide a solid base of evidence for arnicolide D as a lead compound for further development, and act as proof for the viability of drug development from traditional Chinese medicines.

Keywords

NPC; anti-proliferation; apoptosis induction; arnicolide D; cell cycle arrest.

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