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Thymoquinone Induces Apoptosis of Human Renal Carcinoma Caki-1 Cells by Inhibiting JAK2/STAT3 Through Pro-Oxidant Effect

Authors
 In Gyeong Chae  ;  Na-Young Song  ;  Do-Hee Kim  ;  Moo-Yeol Lee  ;  Jung-Min Park  ;  Kyung-Soo Chun 
Citation
 FOOD AND CHEMICAL TOXICOLOGY, Vol.139 : e111253, 2020-05 
Journal Title
 FOOD AND CHEMICAL TOXICOLOGY 
ISSN
 0278-6915 
Issue Date
2020-05
Keywords
JAK2 ; Reactive oxygen species ; Renal cell carcinoma ; STAT3 ; Thymoquinone
Abstract
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.
Full Text
https://www.sciencedirect.com/science/article/pii/S0278691520301411
DOI
10.1016/j.fct.2020.111253
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Song, Na-Young(송나영) ORCID logo https://orcid.org/0000-0001-8658-7049
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/176097
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