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Arnicolide D exerts anti-melanoma effects and inhibits the NF-κB pathway
- Source :
- Phytomedicine. 64:153065
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- 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.
- Subjects :
- Male
Cell cycle checkpoint
Cell Survival
Dacarbazine
Pharmaceutical Science
Antineoplastic Agents
Apoptosis
Lactones
Mice
03 medical and health sciences
0302 clinical medicine
In vivo
Cell Line, Tumor
Drug Discovery
medicine
Animals
Humans
Viability assay
Phosphorylation
Melanoma
030304 developmental biology
Pharmacology
0303 health sciences
Cyclin-dependent kinase 1
Chemistry
Transcription Factor RelA
Cell Cycle Checkpoints
medicine.disease
Mice, Inbred C57BL
Disease Models, Animal
IκBα
Complementary and alternative medicine
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Sesquiterpenes
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 09447113
- Volume :
- 64
- Database :
- OpenAIRE
- Journal :
- Phytomedicine
- Accession number :
- edsair.doi.dedup.....7564d0b02ac80c37a5f0b8c6a35800c2