Thymoquinone induces apoptosis of human renal carcinoma Caki-1 cells by inhibiting JAK2/STAT3 through pro-oxidant effect.,Food and Chemical Toxicology

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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

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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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