Regulation of NF-κB Expression by Thymoquinone; A Role in Regulating Pro-Inflammatory Cytokines and Programmed Cell Death in Hepatic Cancer Cells.

BACKGROUND: The miracle herb Nigella sativa (N. sativa) is a member of the Ranunculaceae family that possesses many properties, such as antioxidant, anticancer, analgesic, antibacterial, and anti-inflammatory. Thymoquinone (TQ) is the primary ingredient that makes up N. sativa, which is responsible for its many properties. So, our research focused on the biological role of TQ and its anticancer activities. METHODS: A wide range of TQ concentrations (50µg/µl, 25µg/ µl, and 12.5µg µl) was prepared and evaluated for their potential regulatory role in cell lines of hepatocellular carcinoma (HepG2 cell line) compared with normal hepatocytes cells, untreated and DMSO-treated cells. RESULTS: The more significant level of LDH obtained after TQ treatment compared to untreated cells provides evidence of the cytotoxic effects of TQ on HepG2 cells. Notably, the normal hepatocyte cells subjected to the same concentrations of TQ showed neglected influence in cell viability rate, indicating the selective regulatory role of TQ in cancer cell proliferation. Interestingly, as a critical mediator of malignancy transformation, the nuclear factor-kappa B expression level (NF-κB) significantly decreased in a time and dose-dependent manner of TQ treatment. Furthermore, we investigated whether TQ regulates the expression of deleted liver cancer 1 (DLC1) and Caspase 3 (Casp3). Notably, the treatment with TQ showed increased expression levels of DLC1 and Casp3 upon treatment. TQ extract sufficiently mediated the secretion of the released pro-inflammatory cytokines from treated cells. This regulation of released cytokines by TQ may affect the activation of NF-κB in treated cells. CONCLUSION: These results indicate that TQ mediates the activation of Casp3, DLC1, and NF-κB, providing a new function of TQ in treating hepatocellular carcinoma (HCC).

Anticancer Properties of Selenium-Enriched Oyster Culinary-Medicinal Mushroom, Pleurotus ostreatus (Agaricomycetes), in Colon Cancer In Vitro.

Mushrooms have become an important way to safely supply the body with the daily needs of organic selenium and they also possess remarkable medicinal properties. In this study, we examined the ability of the Pleurotus ostreatus mushroom to grow in selenium (Se) and its ability to accumulate and convert Se from inorganic form to organic form during growth. Additionally, we achieved the potential anticancer properties of mushroom extract in colon cancer cells using the CaCo-2 cell and the normal human colon mucosal epithelial cell line, NCM-460 cell line. Interestingly, Se-enriched mushroom extract (SME) showed a competitive regulation in colon cancer cell line; CaCo-2 cell line indicated by cell morphology, the number of survived cells, lactate dehydrogenase (LDH) production, and cell viability rate. Moreover, SME treatment regulates the expression profile of the cancer cell proliferation factor Raf-1 and pro-apoptotic related factors P53 and Caspase-3 Furthermore, the production of inflammatory-regulated cytokines, including interleukin 6 (IL-6) and IL-10, increased. At the same time, the level of produced tumor necrosis factor-alpha (TNF-α) markedly decreased in a dose and time-dependent of colon cancer-treated cells. Notably, the purified selenomethionine (SeMe) showed sufficient inhibition of colon cancer proliferation compared with the inorganic form of selenium (sodium selenite) via blocking the Raf/MEK/ERK signaling pathway. In addition, SeMe treatment also stimulated the production of IL-6 and IL-10 while decreasing the production of TNF-α, which plays a crucial role in the necrotic event. Meanwhile, the SeMe treatment showed a neglected cytotoxic effect in the normal colon epithelial cells. Collectively, these findings indicate that the fruiting bodies of Se-enriched mushrooms revealed anti-colon cancer activity via targeting Raf-1 signaling pathway and increasing the production of IL-6 and IL-10.

Single nucleotide polymorphisms of interleukins associated with hepatitis C virus infection in Egypt.

INTRODUCTION: Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). It can cause both acute and chronic hepatitis infection. Based on secretion of required cytokines upon infection, HCV can improve its own RNA and successfully complete the replication cycle. Importantly, single nucleotide polymorphisms (SNPs) are the most common type of genetic variation and have been found to play a critical role in modulation of cellular cytokine production and interaction. METHODOLOGY: A total of 100 blood samples were obtained from HCV patients, and 120 samples were obtained from healthy individuals who served as controls. SNPs of interleukin-10/592 (IL-10/592) and IL-4/589 were investigated for possible connection with HCV infection. Relative expression of IL-4, IL-6, and IL-10 were detected using real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: The polymorphisms of IL-10 revealed a high rate of mutant genotype CC within the location IL-10/592 in HCV patients and controls, which resulted in low secretion of IL-10. Interestingly, the findings here demonstrate a positive association between HCV load of viremia and the mutant genotype IL-4-589/TT accompanied with low expression IL-4 in comparison with IL-6 expression. CONCLUSIONS: These data suggest that the expression of IL-4 is inversely proportional to HCV load of viremia, and this connection is due to the high level of mutant genotype IL-4-589/TT in infected patients located in gene promoter and inhibits gene expression.