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Thymoquinone induces apoptosis of human renal carcinoma Caki-1 cells by inhibiting JAK2/STAT3 through pro-oxidant effect.
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2020-03-09 , DOI: 10.1016/j.fct.2020.111253
In Gyeong Chae 1 , Na-Young Song 2 , Do-Hee Kim 3 , Moo-Yeol Lee 4 , Jung-Min Park 4 , Kyung-Soo Chun 1
Affiliation  

Currently, there are limited effective treatment options for renal cell carcinoma (RCC), due to its poor responses to conventional therapies. Instead of using extrinsic anti-cancer drugs, cancer cell-intrinsic reactive oxygen species (ROS) can be a weapon of RCC treatment. In the present study, we found that the phytochemical thymoquinone (TQ), a bioactive natural product obtained from the black cumin seeds of Nigella sativa, generates intracellular ROS in human renal cancer Caki-1 cells. Treatment of Caki-1 cells with high concentration of TQ up-regulated pro-apoptotic p53 and Bax expression, while downregulated anti-apoptotic Bcl-2 and Bcl-xl expression. Simultaneously, TQ suppressed the pro-oncogenic JAK2/STAT3 pathway, resulting in decreased expression of Bcl-2, Bcl-xl, cyclin D1, cyclin D2, and survivin. Thus, TQ can integrate between apoptosis and the pro-survival JAK2/STAT3 pathway through the Bcl family members, collectively magnifying Caki-1 cell apoptosis. However, treatment with the ROS scavenger N-acetyl cysteine significantly blocked TQ-induced apoptosis as well as incorporated signaling pathways, supporting that its pro-oxidant property is crucial for Caki-1 cell apoptosis. Moreover, TQ reduced the tumor xenograft growth of Caki-1 cells in nude mice. Taken together, these data suggest that TQ is a prominent anti-cancer drug to treat human RCC by enhancing apoptosis through its pro-oxidant nature.

中文翻译:

胸腺醌通过促氧化作用抑制JAK2 / STAT3诱导人肾癌Caki-1细胞凋亡。

目前,由于肾细胞癌(RCC)对常规疗法的反应较差,因此有效的治疗选择有限。代替细胞内在的抗癌药物,癌细胞内在的活性氧(ROS)可以成为RCC治疗的武器。在本研究中,我们发现植物化学胸腺醌(TQ)是一种从黑黑黑孜然种子中提取的生物活性天然产物,可在人肾癌Caki-1细胞中产生细胞内ROS。用高浓度的TQ处理Caki-1细胞可上调促凋亡的p53和Bax表达,而下调抗凋亡的Bcl-2和Bcl-xl表达。同时,TQ抑制促癌的JAK2 / STAT3途径,导致Bcl-2,Bcl-xl,cyclin D1,cyclin D2和survivin的表达降低。从而,TQ可以通过Bcl家族成员整合凋亡和促生存的JAK2 / STAT3途径,共同放大Caki-1细胞的凋亡。但是,用ROS清道夫N-乙酰半胱氨酸治疗可显着阻断TQ诱导的细胞凋亡以及整合的信号传导途径,支持其促氧化剂特性对Caki-1细胞凋亡至关重要。此外,TQ减少了裸鼠中Caki-1细胞的肿瘤异种移植生长。综上所述,这些数据表明,TQ是一种通过增强其抗氧化剂性质来增强细胞凋亡而治疗人RCC的重要抗癌药物。用ROS清道夫N-乙酰半胱氨酸进行的治疗显着阻断了TQ诱导的细胞凋亡以及整合的信号通路,这表明其促氧化剂特性对Caki-1细胞凋亡至关重要。此外,TQ减少了裸鼠中Caki-1细胞的肿瘤异种移植生长。综上所述,这些数据表明,TQ是一种通过增强其抗氧化剂性质来增强细胞凋亡而治疗人RCC的重要抗癌药物。用ROS清道夫N-乙酰半胱氨酸进行的治疗显着阻断了TQ诱导的细胞凋亡以及整合的信号通路,这表明其促氧化剂特性对Caki-1细胞凋亡至关重要。此外,TQ减少了裸鼠中Caki-1细胞的肿瘤异种移植生长。综上所述,这些数据表明,TQ是一种通过增强其抗氧化剂性质来增强细胞凋亡而治疗人RCC的重要抗癌药物。
更新日期:2020-03-09
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