Arnicolide D exerts anti-melanoma effects and inhibits the NF-κB pathway

Melanoma is a lethal cancer. NF-κB has been validated as a molecular target for melanoma treatment. Current therapies for melanoma have limitations. Novel targeted therapeutics are needed. Arnicolide D (Ar-D), a sesquiterpene lactone isolated from the dried whole plant of Centipeda minima (L.) A. Br...

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Published in:Phytomedicine (Stuttgart) 2019-11, Vol.64, p.153065-153065, Article 153065
Main Authors: Zhu, Peili, Zheng, Zhongyu, Fu, Xiuqiong, Li, Junkui, Yin, Chengle, Chou, Jiyao, Wang, Yaping, Liu, Yuxi, Chen, Yingjie, Bai, Jingxuan, Wu, Jiaying, Chen, Sibao, Yu, Zhi-Ling
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Arnicolide D
Cell cycle arrest
Cell Cycle Checkpoints - drug effects
Cell Line, Tumor
Cell Survival - drug effects
Disease Models, Animal
Humans
Lactones - pharmacology
Male
Melanoma
Melanoma - drug therapy
Mice
Mice, Inbred C57BL
NF-κB
Phosphorylation
Sesquiterpenes - pharmacology
Signal Transduction - drug effects
Transcription Factor RelA - antagonists & inhibitors
Transcription Factor RelA - metabolism
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Summary:Melanoma is a lethal cancer. NF-κB has been validated as a molecular target for melanoma treatment. Current therapies for melanoma have limitations. Novel targeted therapeutics are needed. Arnicolide D (Ar-D), a sesquiterpene lactone isolated from the dried whole plant of Centipeda minima (L.) A. Br. et Aschers., has been reported to inhibit NF-κB activity in colorectal cancer cells. To investigate the anti-melanoma effects of Ar-D in vitro and in vivo; and to determine whether Ar-D inhibits the NF-κB pathway in melanoma cells. A B16F10 allograft mouse model and two melanoma cell lines (A375 and B16F10) were used to investigate the anti-melanoma effects of Ar-D in vivo and in vitro. Dacarbazine was used as a positive control. Cell viability was assessed by MTT and crystal violet staining assays. Cell cycle arrest and apoptosis were analyzed by flow cytometry. Protein levels were determined by Immunoblotting. In vivo assays showed that the average tumor weight in Ar-D-treated group (4 mg/kg, i.p, 15 days) was reduced by 53.7%, when compared with the control group. In vitro studies demonstrated that Ar-D reduced cell viability, induced G2/M cell cycle arrest and apoptosis, elevated levels of cell cycle regulatory proteins p53 and p21, and lowered levels of G2/M checkpoint proteins Cdc2 and Cyclin B1 in melanoma cells. Mechanistically, Ar-D inhibited the activity of IKKα/β, the degradation of IκBα, and the phosphorylation and expression of NF-κB p65 in melanoma cells. Ar-D has anti-melanoma effects, and inhibition of the IKK/IκBα/NF-κB p65 pathway is involved in the effects.
ISSN:0944-7113
1618-095X
DOI:10.1016/j.phymed.2019.153065