Engelharquinone suppresses lipopolysaccharide-induced inflammation and proliferation of human liver cancer SMCC7721 cells via inhibition of NF-κB and MAPK signaling pathway

Abstract

Purpose: To investigate the anti-tumor effect of engelharquinone (Eng) on human liver cancer SMCC7721 cells.Methods: GFP-labeled SMCC7721 cells were used to establish a tumor-bearing mice model used for determination of the effect of different concentrations of Eng on tumor growth. The effect of Eng on SMCC7721 cell viability was determined with MTT assay and cell cycle analysis. The anti-inflammatory effect of Eng on lipopolysaccharide (LPS)-treated SMCC7721 cells were determined through assay of pro-inflammatory cytokines. Besides, the effect of Eng on the expressions of mitogen-activated protein kinase (MAPK), toll-like receptor 4 (TLR4), and nuclear factor kappa B (NF-κB) was determined.Results: Cell proliferation was suppressed by different concentrations of Eng in LPS-treated SMCC7721 cells. Treatment of nude mice with Eng at high and low doses resulted in significant suppression of tumor growth and marked increases in percentage survival. Treatment of SMCC7721 cells with LPS upregulated the expressions of NF-κB, p65 and MAPK. However, pre-treatment of the cells with Eng suppressed the LPS-induced upregulation of the NF-κB, p65 and MAPK signaling pathways, and further downregulated the production of inflammatory cytokines in SMCC7721 cells.Conclusion: These results indicate that Eng inhibits LPS-induced inflammation and proliferation of human liver cancer SMCC7721 cells via a mechanism involving regulation of NF-κB and MAPK signaling pathways. Thus, Eng has potentials for the clinical management of inflammatory diseases and liver cancer.
 Keywords: Inflammation, Engelharquinone, Lipopolysaccharide, SMCC7721 cells, Toll-like receptor 4

Strategies for the Construction of Benzobicyclo[3.2.1]octane in Natural Product Synthesis

“…138 possesses moderate antitubercular activity against Mycobacterium tuberculosis 90–221387. A recent report showed that 138 also inhibited LPS‐induced inflammation and proliferation of human liver cancer SMCC7721 cells via a mechanism involving the regulation of NF‐κB and MAPK signaling pathways [44b] . While isolated 138 and 139 were optically active, an enantioselective total synthesis from Ohmori and Suzuki group suggests that both may naturally occur in a scalemic form [46]…”