Although enormous achievements have been made in targeted molecular therapies against hepatocellular carcinoma (HCC), the treatments can only prolong the life of patients with extrahepatic metastases. We evaluated thymoquinone (TQ), a compound from Nigella sativa Linn., for its anti-cancer effect on SK-Hep1 cells and HCC-xenograft nude mice. TQ effectively triggered cell death and activated p38 and extracellular signal-regulated kinases (Erk) pathways up to 24 h after treatment in cells. TQ-induced cell death was reversed by p38 inhibitor; however, it was enhanced by si-Erk. The caspase3 activation and TUNEL assay revealed a stronger toxic effect upon co-treatment with TQ and si-Erk. Our study suggested that phosphorylation of p38 in SK-Hep1 cells constituted the major factor leading to cell apoptosis, whereas phosphorylation of Erk led to drug resistance. Furthermore, TQ therapeutic effect was improved upon Erk inhibition in HCC-xenograft nude mice. TQ could present excellent anti-HCC potential under suitable p-Erk inhibiting conditions.
Keywords: Erk; SK-Hep1 cells; hepatocellular carcinoma; p38; thymoquinone.
© 2021 The Authors. Environmental Toxicology published by Wiley Periodicals LLC.