Arnicolide D, from the herb <i>Centipeda minima,</i> Is a Therapeutic Candidate against Nasopharyngeal Carcinoma
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 <i>Centipeda minima</i> extract (CME) exhibited anti-cancer effects in human NPC cell lines....
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MDPI AG
2019-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/10/1908 |
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| author | Rui Liu Brandon Dow Chan Daniel Kam-Wah Mok Chi-Sing Lee William Chi-Shing Tai Sibao Chen |
| author_facet | Rui Liu Brandon Dow Chan Daniel Kam-Wah Mok Chi-Sing Lee William Chi-Shing Tai Sibao Chen |
| author_sort | Rui Liu |
| collection | DOAJ |
| description | 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 <i>Centipeda minima</i> extract (CME) exhibited anti-cancer effects in human NPC cell lines. Arnicolide C and arnicolide D are sesquiterpene lactones isolated from <i>Centipeda minima</i>. 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 G<sub>2</sub>/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. |
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| series | Molecules |
| spelling | doaj.art-28300426584c4060a425886bd0f6a9352022-12-21T23:57:31ZengMDPI AGMolecules1420-30492019-05-012410190810.3390/molecules24101908molecules24101908Arnicolide D, from the herb <i>Centipeda minima,</i> Is a Therapeutic Candidate against Nasopharyngeal CarcinomaRui Liu0Brandon Dow Chan1Daniel Kam-Wah Mok2Chi-Sing Lee3William Chi-Shing Tai4Sibao Chen5State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen 518057, ChinaDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom 999077, Hong Kong, ChinaState Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen 518057, ChinaDepartment of Chemistry, The Hong Kong Baptist University, Kowloon Tong 999077, Hong Kong, ChinaState Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen 518057, ChinaState Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen 518057, ChinaNasopharyngeal 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 <i>Centipeda minima</i> extract (CME) exhibited anti-cancer effects in human NPC cell lines. Arnicolide C and arnicolide D are sesquiterpene lactones isolated from <i>Centipeda minima</i>. 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 G<sub>2</sub>/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.https://www.mdpi.com/1420-3049/24/10/1908arnicolide DNPCanti-proliferationcell cycle arrestapoptosis induction |
| spellingShingle | Rui Liu Brandon Dow Chan Daniel Kam-Wah Mok Chi-Sing Lee William Chi-Shing Tai Sibao Chen Arnicolide D, from the herb <i>Centipeda minima,</i> Is a Therapeutic Candidate against Nasopharyngeal Carcinoma Molecules arnicolide D NPC anti-proliferation cell cycle arrest apoptosis induction |
| title | Arnicolide D, from the herb <i>Centipeda minima,</i> Is a Therapeutic Candidate against Nasopharyngeal Carcinoma |
| title_full | Arnicolide D, from the herb <i>Centipeda minima,</i> Is a Therapeutic Candidate against Nasopharyngeal Carcinoma |
| title_fullStr | Arnicolide D, from the herb <i>Centipeda minima,</i> Is a Therapeutic Candidate against Nasopharyngeal Carcinoma |
| title_full_unstemmed | Arnicolide D, from the herb <i>Centipeda minima,</i> Is a Therapeutic Candidate against Nasopharyngeal Carcinoma |
| title_short | Arnicolide D, from the herb <i>Centipeda minima,</i> Is a Therapeutic Candidate against Nasopharyngeal Carcinoma |
| title_sort | arnicolide d from the herb i centipeda minima i is a therapeutic candidate against nasopharyngeal carcinoma |
| topic | arnicolide D NPC anti-proliferation cell cycle arrest apoptosis induction |
| url | https://www.mdpi.com/1420-3049/24/10/1908 |
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