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

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.

Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways

“…The whole plant has been employed as a TCM for millennia and is commonly treatment for indications such as rhinitis, sinusitis, cough, headache, swelling, and allergy (11). Phytochemical research has demonstrated CM mainly contain phenolic acids (e.g., isochlorogenic acid A and isochlorogenic acid C), flavonoids, and sesquiterpene lactones [e.g., Brevilin A, Arnicolide D; (12)(13)(14)(15)(16)]. Reports suggest that Centipeda minima extracts (CME) possess anti-inflammatory (17), anti-bacterial (18,19), and anti-allergic (20) effects.…”

“…Reports suggest that Centipeda minima extracts (CME) possess anti-inflammatory (17), anti-bacterial (18,19), and anti-allergic (20) effects. Previous studies have demonstrated the anti-cancer effects of CME, and compounds extracted from CM, in various cancers including nasopharyngeal carcinoma (13,14,21,22), leukemia (23), glioblastoma (24), lung cancer (25), and colon cancer (26), however, the effects of CME on breast cancer have to date, not been demonstrated.…”

Arnicolide D Inhibits Triple Negative Breast Cancer Cell Proliferation by Suppression of Akt/mTOR and STAT3 Signaling Pathways

“…International Publisher effects, in cancers including colon carcinoma [10], melanoma [11], and nasopharyngeal carcinoma [12]. However, there have been no reports on the effects of AD in TNBC.…”

“…Thus, natural products are attracting increasing amounts of attention from researchers in the cancer field. Arnicolide D (AD) (Figure 1 ), a natural sesquiterpene lactone extracted from Centipeda minima 9 , has been reported to exhibit anti-bacterial 9 and anti-cancer effects, in cancers including colon carcinoma 10 , melanoma 11 , and nasopharyngeal carcinoma 12 . However, there have been no reports on the effects of AD in TNBC.…”

Brevilin A Isolated from Centipeda minima Induces Apoptosis in Human Gastric Cancer Cells via an Extrinsic Apoptotic Signaling Pathway

“…In addition, it has recently been reported that certain phytochemical constituents of CMX have potential utility for the development of anticancer agents [3]. For example, arnicolide D isolated from CMX has been demonstrated to have anticancer effects against human nasopharyngeal carcinoma cells [4]. Previous studies have also reported that brevilin A, of which CMX is an abundant source, shows anticancer effects on a range of different cancer cell lines, including those of lung, breast, liver, and colon cancers and melanoma [5][6][7].…”