Thymoquinone induces apoptosis of human renal carcinoma Caki-1 cells by inhibiting JAK2/STAT3 through pro-oxidant effect

In Gyeong Chae, Na Young Song, Do Hee Kim, Moo Yeol Lee, Jung Min Park, Kyung Soo Chun

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14 Citations (Scopus)

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.

Original languageEnglish
Article number111253
JournalFood and Chemical Toxicology
Volume139
DOIs
Publication statusPublished - 2020 May

Bibliographical note

Funding Information:
This research was supported by the Bio & Medical Technology Development Program of the NRF ( NRF-2015M3A9B6074045 ) and the Medical Research Center Program ( NRF-2016R1A5A2008630 ) funded by the Ministry of Science, ICT and Future Planning (MSIP) .

Publisher Copyright:
© 2020 Elsevier Ltd

All Science Journal Classification (ASJC) codes

  • Food Science
  • Toxicology

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