title: Oxidative stress-mediated intrinsic apoptosis in human promyelocytic leukemia HL-60 cells induced by organic arsenicals.
abstract: Arsenic trioxide has shown the excellent therapeutic efficiency for acute promyelocytic leukemia. Nowadays, more and more research focuses on the design of the arsenic drugs, especially organic arsenicals, and on the mechanism of the inducing cell death. Here we have synthesized some organic arsenicals with Schiff base structure, which showed a better antitumor activity for three different kinds of cancer cell lines, namely HL-60, SGC 7901 and MCF-7. Compound 2a (2-(((4-(oxoarsanyl)phenyl)imino)methyl)phenol) and 2b (2-methoxy-4-(((4-(oxoarsanyl)phenyl)imino)methyl)phenol) were chosen for further mechanism study due to their best inhibitory activities for HL-60 cells, of which the half inhibitory concentration (IC50) were 0.77 μM and 0.51 μM, respectively. It was illustrated that 2a or 2b primarily induced the elevation of reactive oxygen species, decrease of glutathione level, collapse of mitochondrial membrane potential, release of cytochrome c, activation of Caspase-3 and apoptosis, whereas all of the phenomena can be eliminated by the addition of antioxidants. Therefore, we concluded that compound 2a and 2b can induce the oxidative stress-mediated intrinsic apoptosis in HL-60 cells. Both the simplicity of structure with Schiff base group and the better anticancer efficiency demonstrate that organic arsenicals are worthy of further exploration as a class of potent antitumor drugs.
authors.affiliation: State Key Laboratory of Virology, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China.
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Fan
authors.affiliation: School of Chemistry and Materials Science, Hubei Engineering University, Xiaogan 432000, P. R. China.
authors.forename: Xin-You
authors.initials: XY
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China.
authors.forename: Yu-Jiao
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Virology, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China.
authors.forename: Feng-Lei
authors.initials: FL
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Virology, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P. R. China.|School of Chemistry and Materials Science, Hubei Engineering University, Xiaogan 432000, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D045304:Cytochromes c / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001152:Arsenicals; D010087:Oxides; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D053148:Caspase 3; D000077237:Arsenic Trioxide