Uvangoletin induces mitochondria-mediated apoptosis in HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances

Zheng,Zhuanzhen; Qiao,Zhenhua; Gong,Rong; Wang,Yalin; Zhang,Yiqun; Ma,Yanping; Zhang,Li; Lu,Yujin; Jiang,Bo; Li,Guoxia; Dong,Chunxia; Chen,Wenliang

doi:10.3892/or.2015.4443

Uvangoletin induces mitochondria-mediated apoptosis in HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances

Authors:
- Zhuanzhen Zheng
- Zhenhua Qiao
- Rong Gong
- Yalin Wang
- Yiqun Zhang
- Yanping Ma
- Li Zhang
- Yujin Lu
- Bo Jiang
- Guoxia Li
- Chunxia Dong
- Wenliang Chen
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Affiliations: Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, P.R. China, Shanxi Academy of Medical Sciences, Shanxi University Hospital, Taiyuan 030001, P.R. China, Department of Hematology, the Second People's Hospital of Shanxi Province, Taiyuan 030001, P.R. China
Published online on: November 25, 2015 https://doi.org/10.3892/or.2015.4443
Pages: 1213-1221

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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.

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