Thymoquinone suppresses the proliferation of renal cell carcinoma cells via reactive oxygen species‐induced apoptosis and reduces cell stemness

Abstract

Thymoquinone is a phytochemical compound isolated from Nigella sativa and has various biological effects, including anti‐inflammation, antioxidation, and anticancer. Here, we further investigated the anticancer effects and associated molecular mechanism of 2‐methyl‐5‐isopropyl‐1,4‐benzoquinone (thymoquinone) on human renal carcinoma cell lines 786‐O and 786‐O‐SI3 and transitional carcinoma cell line BFTC‐909. Results showed that thymoquinone significantly reduced cell viability, inhibited the colony formation of renal cancer cells, and induced cell apoptosis and mitochondrial membrane potential change in both cancer cells. In addition, thymoquinone also triggered the production of reactive oxygen species (ROS) and superoxide and the activation of apoptotic and autophagic cascade. ROS inhibition suppressed the caspase‐3 activation and restored the decreased cell viability of 786‐O‐SI3 in response to thymoquinone. Autophagy inhibition did not restore the cell viability of 786‐O‐SI3 suppressed by thymoquinone. Moreover, thymoquinone suppressed the cell sphere formation and the expression of aldehyde dehydrogenase, Nanog, Nestin, CD44, and Oct‐4 in 786‐O‐SI3 cells. The tumor‐bearing model showed that thymoquinone in vivo inhibited the growth of implanted 786‐O‐SI3 cell. All these findings indicate that thymoquinone inhibits the proliferation of 786‐O‐SI3 and BFTC‐909 cell possibly due to the induction of ROS/superoxide and the consequent apoptosis, suggesting that thymoquinone may be a potential anticancer supplement for genitourinary cancer.

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

“…TQ-generated ROS causes oxidative stress, mitochondrial and nuclear damage, and subsequent cell-death. This has been demonstrated in many different cancer cells including those from adult T-cell leukemia [33], prostate [34], hepatocellular carcinoma (HCC) [35], skin [36,37], breast [38], kidney [39,40], renal cell carcinoma [39], and ovarian cancer [41]. The pro-oxidant property of TQ is also observed to modulate the ionic status of the transition metal ion copper, so as to promote cell death in prostate cancer cells [34].…”

Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

“…ROS is an important signaling molecule in various vital cellular processes, including cell apoptosis, autophagy, proliferation, and differentiation [41]. Many studies have found that excessive accumulation of intracellular ROS caused irreversible cellular damage leading to autophagy and/or apoptosis [42,43]. Chao…”

Genetic, biochemical and histopathological evaluations of thymoquinone on male reproduction system damaged by paclitaxel in Wistar rats

“…Studies have shown that THY significantly reduced the expression of caspase‐3 and bax and significantly increased the expression of Bcl‐2 in kidney tissue. In fact, THY prevents induction of apoptosis in cells by removing ROS (Liou et al., 2019). One of the most important destructive effects of free radicals is lipid peroxidation, which causes cell membrane damage.…”