Effects of Thymoquinone on IL-6 Gene Expression and Some Cellular Signaling Pathways in Prostate Cancer PC3 Cells

Abstract

Background: Thymoquinone (TQ), a bioactive compound, has many pharmacological actions especially anticancer effects. Prostate cancer (PC) is one of the most common malignancies among males in the world. Objectives: The current study aimed at evaluating the effects of TQ treatment on interleukin-6 (IL-6) expression, IL-6 secretion, cell viability, phosphorylated extracellular signal–regulated kinases (pERK1/2), phosphorylated AKT (pAKT), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) signaling pathways in human prostate cancer PC3 cells. Materials and Methods: PC3 cells were cultured in different concentrations of TQ for 48 hours. Cell viability, expression, and secretion of IL-6 were assessed by MTT assay, real-time quantitative polymerase chain reaction (RT-q PCR) analysis, and the enzyme-linked immunosorbent assay (ELISA) technique, respectively. The changes of pERK1/2, pAKT, and pSTAT3 were determined using Western blot procedure. Results: Treatment with TQ caused the reduction of viability (inhibitory concentration [IC50] = 45 µM) and survival in PC3 cells. RT-q PCR had a significant reduction (P < 0.05) in IL-6 gene expression compared with the control cells (50%, 59%, 68%, and 70% at 30, 40, 45, and 50 µM of TQ, respectively). TQ treatment resulted in a significant decline (P < 0.05) in the secretion of IL-6 compared with the control cells (56.89%, 71.12%, 84.32%, and 85.89% at 30, 40, 45, and 50 µM of TQ, respectively). Western blot showed a reduction in the phosphorylated STAT3, AKT, and ERK proteins. Conclusions: The obtained results suggested that TQ can effectively reduce IL-6 signaling pathways (pSTAT3, pAKT, and pERK1/2). Also, TQ can decrease IL-6 gene expression, which leads to the reduction of cell proliferation and viability. Therefore, TQ may be beneficial to treat prostate cancer.