Thymoquinone exerts anti-tumor activities on human hepatocellular carcinoma cells: role of angiogenesis-related genes VCAN, Grb2 and EZH2
a Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia.
b Biochemistry Department, Faculty of Science, Ain Shams University, Abbassia 11566, Cairo, Egypt.
c Department of Basic Medical Sciences, College of Medicine and Health Sciences, Hadhramout University, Mukalla, Yemen.
d Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia.
Human hepatocellular carcinoma (HCC) is the most prevalent and recurrent type of primary adult liver cancer without any effective therapy. Thus, there is an increase demands for finding new drugs and treatment strategies with selective and potent effects towards HCC. Plant-derived compounds acting as anti-cancer agents can induce apoptosis through targeting several signaling pathways. Thymoquinone (TQ), the major biologically active compound of the black seed oil (Nigella sativa) has demonstrated inhibitory activities on various cancers by targeting several pathways. In the present study, we have evaluated the molecular mechanisms that underlie the anti-proliferative, anti-metastatic, and pro-apoptotic activities exerted by TQ on liver cancer cell lineHepG2, a well-documented HCC in vitro model. Cell proliferation was determined by WST-1 assay, apoptosis rate was assessed by flow cytometry using annexin-V/7AAD staining, wound healing assay to investigate the metastasis, and the expression of target genes was assessed by Real-time RT–PCR analysis. We found that TQ significantly reduced HepG2 cell viability and induced apoptosis in a dose-dependent manner. Migration of HepG2 cells was suppressed in response to TQ. Moreover, TQ decreased the expression of several angiogenesis-related genes including versican (VCAN), growth factor receptor-bound protein 2 (Grb2), and the histone methyltransferase for lysine 27 of histone 3 (EZH2). The findings suggest that TQ exerts inhibitory effects on HCC most likely through targeting key genes involved in the invasiveness and metastatic activities of HCC cells and also suggest that TQ could be used in future as potential anti-HCC candidate in chemotherapy.