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Fisetin Inhibits Cell Proliferation and Induces Apoptosis via JAK/STAT3 Signaling Pathways in Human Thyroid TPC 1 Cancer Cells
Biotechnology and Bioprocess Engineering ( IF 2.5 ) Pub Date : 2020-04-23 , DOI: 10.1007/s12257-019-0326-9
Ying Liang , Deyu Kong , Yi Zhang , Siqi Li , Yan Li , Anuradha Ramamoorthy , Junfeng Ma

Thyroid cancer is the most important malignant tumor reported in human populations where, its treatment remains undeveloped. Fisetin, a plant flavonoid exhibits several pharmacological properties like antioxidant, anti-inflammatory, and anticancer function. In the existing study, we assessed fisetin mediated cytotoxic effects and action potential of fisetin on cell proliferation in TPC-1 human cancer cells. Also, examined the apoptosis in TPC-1 cells by reactive oxygen species (ROS) generation, the mitochondrial membrane potential (MMP) and apoptotic morphological changes through AO/EtBr staining. Additionally, we analyzed the effects of fisetin through ELISA analysis to evaluate the caspases expression and studied JAK 1 and STAT3 signaling molecule in TPC1 cells. Our results demonstrated that fisetin stimulated apoptosis, which confirmed through reduced cell viability, improved ROS generation, altered MMP and cell cycle phases in TPC-1 cells. Further, the fisetin up-regulated the expression of caspase (3, 8, and 9) expressions in TPC-1 cells. Also, we observed the fisetin down-regulated the JAK 1 and STAT3 expression in TPC1 cells. Thus, the fisetin induced apoptosis in TPC-1 cells by the induction of oxidative damage and enhanced caspases expression by down-regulating JAK 1 and STAT3 signaling molecules. Hence, the fisetin would be considered as a beneficial therapeutic agent for the thyroid cancer treatment.



中文翻译:

Fisetin通过人甲状腺TPC 1癌细胞中的JAK / STAT3信号通路抑制细胞增殖并诱导凋亡。

甲状腺癌是人类中最重要的恶性肿瘤,其治疗尚不成熟。Fisetin是一种植物类黄酮,具有多种药理特性,例如抗氧化剂,抗炎和抗癌功能。在现有研究中,我们评估了Fisetin介导的细胞毒性作用以及Fisetin对TPC-1人癌细胞中细胞增殖的作用潜力。此外,通过AO / EtBr染色检查了活性氧(ROS)的产生,线粒体膜电位(MMP)和细胞凋亡形态变化,从而检测了TPC-1细胞的凋亡。此外,我们通过ELISA分析了非瑟酮的作用,以评估半胱氨酸蛋白酶的表达,并研究了TPC1细胞中JAK 1和STAT3信号分子。我们的结果表明,非瑟汀可刺激细胞凋亡,通过降低细胞活力,改善ROS生成,改变MPC和TPC-1细胞的细胞周期阶段证实了这一点。此外,非瑟酮上调了TPC-1细胞中caspase(3、8和9)的表达。此外,我们观察到非瑟酮下调TPC1细胞中的JAK 1和STAT3表达。因此,非瑟酮通过下调JAK 1和STAT3信号分子,通过诱导氧化损伤和增强的胱天蛋白酶表达来诱导TPC-1细胞凋亡。因此,非瑟定将被认为是用于甲状腺癌治疗的有益治疗剂。我们观察到非瑟酮下调了TPC1细胞中JAK 1和STAT3的表达。因此,fisetin通过下调JAK 1和STAT3信号分子,通过诱导氧化损伤和增强的胱天蛋白酶表达来诱导TPC-1细胞凋亡。因此,非瑟定将被认为是用于甲状腺癌治疗的有益治疗剂。我们观察到非瑟酮下调了TPC1细胞中JAK 1和STAT3的表达。因此,fisetin通过下调JAK 1和STAT3信号分子,通过诱导氧化损伤和增强的胱天蛋白酶表达来诱导TPC-1细胞凋亡。因此,非瑟定将被认为是用于甲状腺癌治疗的有益治疗剂。

更新日期:2020-04-23
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