title: Uvangoletin induces mitochondria-mediated apoptosis in HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances.
abstract: This study investigated the cytotoxic effect of uvangoletin on HL-60 cells, and the effects of uvangoletin on myelosuppression, leucopenia, gastrointestinal tract disturbances and the possible cytotoxic mechanisms by using CCK-8, flow cytometry, western blot, xenograft, cyclophosphamide-induced leucopenia, copper sulfate-induced emesis and ethanol-induced gastric mucosal lesions assays. The results of CCK-8, flow cytometry and western blot assays indicated that uvangoletin showed the cytotoxic effect on HL-60 cells and induced the apoptosis of HL-60 cells by downregulating the expression levels of anti-apoptotic proteins (Survivin, Bcl-xl and Bcl-2), upregulating the expression levels of pro-apoptotic proteins (Smac, Bax, Bad, c-caspase-3 and c-caspase-9), and promoting the release of cytochrome c from mitochondria to cytoplasm. Further, the results of xenograft assay suggested that uvangoletin inhibited the HL-60-induced tumor growth without adverse effect on body weight of nude mice in vivo by regulating the expression levels of above apoptotic proteins. The results indicated that the reductions of WBCs count and thighbone marrow granulocytes percentage in cyclophosphamide-induced leucopenia assay, the incubation period and number of emesis in copper sulfate-induced emesis assay and the gastric mucosal lesions in ethanol-induced gastric mucosal lesions assay were not exacerbated or reversed by uvangoletin. In conclusion, the research preliminarily indicated that uvangoletin induced apoptosis of HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances, and the pro-apoptotic mechanisms may be related to mitochondria-mediated apoptotic pathway.
authors.affiliation: Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, P.R. China.
authors.forename: Zhuanzhen
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, P.R. China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Shanxi Academy of Medical Sciences, Shanxi University Hospital, Taiyuan 030001, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gong
authors.affiliation: Department of Hematology, the Second People's Hospital of Shanxi Province, Taiyuan 030001, P.R. China.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, P.R. China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, P.R. China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Shanxi Academy of Medical Sciences, Shanxi University Hospital, Taiyuan 030001, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Shanxi Academy of Medical Sciences, Shanxi University Hospital, Taiyuan 030001, P.R. China.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, P.R. China.
authors.forename: Guoxia
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, P.R. China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, P.R. China.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D001855:Bone Marrow Diseases / Q000139:chemically induced; D010856:Columbidae; D019327:Copper Sulfate / Q000633:toxicity; D003520:Cyclophosphamide / Q000633:toxicity; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D000431:Ethanol / Q000633:toxicity; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects*; D009325:Nausea / Q000139:chemically induced; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D004365:Drugs, Chinese Herbal; D009363:Neoplasm Proteins; C000611553:uvangoletin; D000431:Ethanol; D003520:Cyclophosphamide; D019327:Copper Sulfate