Thymoquinone attenuates phosphorylation of AKT to inhibit kidney cancer cell proliferation

Thymoquinone (Tq) is an active compound from Nigella sativa which is used in traditional medicine. The effect of Tq on kidney cancer and the pathway of action remain unproven. Herein, we report the anticancer properties of Tq on kidney cancer cells. Tq demonstrated anti-proliferative effects in A498 cells with a GI(50) value of 40.07 mu M and Caki-1 cells with a GI50 of 51.04 mu M by the MTT assay. Tq exhibited nuclear fragmentation and inhibited trans-endothelial migration of A498 and Caki-1 cells in a dose-responsive manner. Time-dependent increase in Annexin V-positive cells and sub-G(0)/G(1) cell population was observed post-Tq treatment. The compound increased Bax protein levels and reduced Bcl-2 protein levels dose dependently in cells, thereby favoring apoptosis. Tq decreased the phosphorylation of Akt in both kidney cell types. The results suggest effective anticancer activity of Tq on kidney cancer cells which may be mediated by the Akt pathway. Practical applications Results from the current investigation will through more light on the mechanistic pathway of Tq activity on the inhibition of kidney cancer cell proliferation. The output of this preclinical in vitro study may be translated into better chemotherapeutics of Tq and its analogs to treat kidney cancer. However, a detailed investigation on in vivo models is recommended.