Arnicolide D exerts anti-melanoma effects and inhibits the NF-κB pathway
- Phytomedicine. 2019 Nov:64:153065. doi: 10.1016/j.phymed.2019.153065.
- 1. Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China; Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China.
- 2. Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
- 3. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China. Electronic address: [email protected].
- 4. Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China; Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China. Electronic address: [email protected].
Background: 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.
Purpose: 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.
Methods: 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.
Results: 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.
Conclusion: Ar-D has anti-melanoma effects, and inhibition of the IKK/IκBα/NF-κB p65 pathway is involved in the effects.