Thymoquinone exerts anti-tumor activities on human hepatocellular carcinoma cells: role of angiogenesis-related genes VCAN, Grb2 and EZH2

Abstract

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

Thymoquinone, as a Novel Therapeutic Candidate of Cancers

“…In the HepG2 human hepatocellular carcinoma cell line, different concentrations of TQ (10, 30 and 50 µM) have notably reduced viability, induced apoptosis, and suppressed HepG2 cells’ migration and invasion ability in a dose-dependent manner. It also reduced angiogenesis by downregulating significant angiogenic genes such as versican (VCAN), the growth factor receptor-binding protein 2 (Grb2), and enhancer of zeste homolog 2 (EZH2), which participates in histone methylation [ 99 ]. An in vivo study has confirmed that TQ reduced oxidative stress, prevented necrosis, enhanced regeneration, and downregulated the expression of miR-206b-3p in the liver tissue of mice with Ehrlich acid solid tumor after intraperitoneal injection with 10 mg/kg TQ for 4 weeks (five doses/week) [ 100 ].…”

Thymoquinone in Cancers Therapy

“…In the HepG2 human hepatocellular carcinoma cell line, different concentrations of TQ (10, 30 and 50 µM) have notably reduced viability, induced apoptosis, and suppressed HepG2 cells' migration and invasion ability in a dose-dependent manner. It also reduced angiogenesis by downregulating significant angiogenic genes such as versican (VCAN), the growth factor receptor-binding protein 2 (Grb2), and enhancer of zeste homolog 2 (EZH2), which participates in histone methylation [99]. An in vivo study has confirmed that TQ reduced oxidative stress, prevented necrosis, enhanced regeneration, and downregulated the expression of miR-206b-3p in the liver tissue of mice with Ehrlich acid solid tumor after intraperitoneal injection with 10 mg/kg TQ for 4 weeks (five doses/week) [100].…”