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.