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Quinalizarin induces cycle arrest and apoptosis via reactive oxygen species‐mediated signaling pathways in human melanoma A375 cells
Author(s) -
Luo YingHua,
Li JinQian,
Zhang Yi,
Wang JiaRu,
Xu WanTing,
Zhang Yu,
Feng YuChao,
Li ShiZe,
Jin ChengHao
Publication year - 2019
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21582
Subject(s) - apoptosis , viability assay , biology , cell cycle , microbiology and biotechnology , mapk/erk pathway , cell growth , reactive oxygen species , signal transduction , cyclin b1 , chemistry , biochemistry , cyclin dependent kinase 1
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.