Thymoquinone (TQ), a compound isolated from black seed oil (nigella sativa), has been reported to possess anti-inflammatory and anticancer activities. However, the molecular mechanisms underlying the anticancer effects of TQ in renal cell carcinoma (RCC) remain poorly understood. This study revealed that treatment with TQ significantly reduced the cell viability and induced apoptosis in Caki cells as evidenced by the induction of p53 and Bax, release of cytochrome c, cleavage of caspase-9, and -3 and PARP and the inhibition of Bcl-2 and Bcl-xl expression. TQ inhibited the constitutive phosphorylation of signal transducer and activator of transcription-3 (STAT3) in Caki cells by blocking the phosphorylation of upstream Janus-activated kinase-2 (JAK2) kinases. Moreover, TQ attenuated the expression of STAT3 target gene products, such as survivin, cyclin D1, and D2. Since ROS is a universal entity mediating apoptosis, we examined whether TQ induced apoptosis via ROS formation. Treatment with TQ generated ROS in these renal cancer cells. Pretreatment of cells with ROS scavenger N-acetyl cysteine (NAC) abrogated the inhibitory effect of TQ on the JAK2/STAT3 signaling and rescued cells from TQ-induced apoptosis by blocking the induction of p53, and the cleavage of caspase-3, -9 and PARP in Caki cells. In conclusion, TQ induced apoptosis in Caki cells via generation of ROS, induction of p53, activation of caspases and inhibition of STAT3 signaling pathway.

Citation Format: In Gyeong Chae, Kyung-Soo Chun. Thymoquinone induces apoptosis through inhibition of JAK2/STAT3 signaling via production of ROS in human renal cancer Caki cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4844.