Dihydroartemisinin increases apoptosis of colon cancer cells through targeting Janus kinase 2/signal transducer and activator of transcription 3 signaling

Dihydroartemisinin increases apoptosis of colon cancer cells through targeting Janus kinase 2/signal transducer and activator of transcription 3 signaling
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DOI:
10.3892/ol.2017.7502
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发表时间:
2018-02-01
期刊:
影响因子:
2.9
通讯作者:
Liu, Xiaodong
Liu, Xiaodong
中科院分区:
医学4区
文献类型:
--
作者:
Wang, Dongsheng;Zhong, Bei;Liu, Xiaodong

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双氢青蒿素是青蒿素的一种衍生物,在治疗疟疾方面效果显著。双氢青蒿素已被证实在多种类型的肿瘤动物模型中具有抑制作用,表明它具有抗肿瘤作用。本研究的目的是分析双氢青蒿素的潜在抗癌作用,特别是对结肠癌细胞凋亡的影响。本研究证实,双氢青蒿素可抑制结肠癌细胞的存活率,促进细胞凋亡,增加B细胞淋巴瘤相关X蛋白的表达,提高caspase-3/9活性,降低聚(ADP-核糖)聚合酶水平,减少细胞外信号调节激酶的磷酸化,增加c-jun氨基末端激酶和p38丝裂原活化蛋白激酶的磷酸化。相反,双氢青蒿素抑制结肠癌细胞中Janus kinase2(JAK2)和信号转导与转录激活子3(STAT3)的磷酸化。这些结果表明,双氢青蒿素潜在的抗癌作用可能是通过靶向JAK2/STAT3信号通路来促进结肠癌细胞的凋亡。
As a derivative of artemisinin, dihydroartemisinin is effective in the treatment of malaria. Dihydroartemisinin has been identified to possess inhibitory effects in numerous types of animal model with tumors, indicating that it has an antineoplastic effect. The aim of the present study was to analyze the potential anticancer effects of dihydroartemisinin, particularly its effect on apoptosis of colon cancer cells. In the present study, it was identified that dihydroartemisinin inhibited cell viability, promoted cell apoptosis, increased B-cell lymphoma-2-associated X-protein expression, increased caspase-3/9 activities, decreased poly(ADP-ribose) polymerase levels, decreased phosphorylation of extracellular-signal-regulated kinase, and increased phosphorylation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase in colon cancer cells. Conversely, the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was suppressed by dihydroartemisinin in colon cancer cells. These results demonstrate that the potential anticancer effects of dihydroartemisinin may increase apoptosis of colon cancer cells through targeting JAK2/STAT3 signaling.