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Quinalizarin induces cycle arrest and apoptosis via reactive oxygen species-mediated signaling pathways in human melanoma A375 cells
- Source :
- Drug development researchREFERENCES. 80(8)
- Publication Year :
- 2019
-
Abstract
- Quinalizarin, a bioactive and highly selective compound, is known to promote apoptosis in colon and lung cancer cells. However, studies evaluating quinalizarin-induced apoptosis in melanoma cells have not been conducted. In the present study, we investigated the underlying mechanisms of antimelanoma activity of quinalizarin in human melanoma A375 cells. The MTT assay and Trypan blue staining were used to evaluate the cell viability. The flow cytometry was used to detect cell cycle, apoptosis and reactive oxygen species (ROS). Western blot was used to detect the expression of cell cycle and apoptosis-related proteins, MAPK, and STAT3. The results revealed a significant dose and time dependent effect of quinalizarin on inhibiting proliferation in three kinds of human melanoma cells, and had no significant toxic effects on normal cells. Moreover, quinalizarin triggered G2/M phase cell arrest by modulating the protein expression levels of CDK 1/2, cyclin A, cyclin B, p21 and p27, and induced apoptosis by down-regulating the antiapoptotic protein Bcl-2 and upregulating the proapoptotic protein BAD, leading to the activation of caspase-3 and PARP in the caspase cascade in A375 cells. Quinalizarin treatment led to apoptosis of A375 cells via activation of MAPK and inhibition of STAT3 signaling pathways. In addition, quinalizarin increased the level of ROS, but ROS scavenger NAC inhibited quinalizarin-induced apoptosis by regulating MAPK and STAT3 signaling pathways. In summary, quinalizarin induces cell cycle arrest and apoptosis via ROS-mediated MAPK and STAT3 signaling pathways in human melanoma A375 cells, and quinalizarin may be used as a novel and effective antimelanoma therapeutic.
- Subjects :
- MAPK/ERK pathway
Cell cycle checkpoint
Cell Survival
Cyclin A
Cyclin B
Anthraquinones
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cyclin-dependent kinase
Cell Line, Tumor
Drug Discovery
Humans
Melanoma
Cell Proliferation
Membrane Potential, Mitochondrial
Quinalizarin
biology
Chemistry
Cell Cycle Checkpoints
Cell cycle
Mitochondria
Gene Expression Regulation, Neoplastic
Apoptosis
030220 oncology & carcinogenesis
biology.protein
Cancer research
Apoptosis Regulatory Proteins
Reactive Oxygen Species
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 10982299
- Volume :
- 80
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Drug development researchREFERENCES
- Accession number :
- edsair.doi.dedup.....65791c4d415724c1985915f1400ae3c9