title: CXC195 suppresses proliferation and inflammatory response in LPS-induced human hepatocellular carcinoma cells via regulating TLR4-MyD88-TAK1-mediated NF-κB and MAPK pathway.
abstract: CXC195 showed strong protective effects in neuronal apoptosis by exerting its antioxidant activity. However, the anti-cancer effects of CXC195 is still with limited acquaintance. Here, we investigated the role of CXC195 in lipopolysaccharide (LPS)-induced human hepatocellular carcinoma (HCC) cells lines (HepG2) and the possible signaling pathways. CXC195 exhibited significant anti-proliferative effect and induced cell cycle arrest in LPS-induced HepG2 cells. In addition, CXC195 suppressed the release of pro-inflammatory mediators in LPS-induced HepG2 cells, including TNF-α, iNOS, IL-1β, IL-6, CC chemokine ligand (CCL)-2, CCL-22 and epidermal growth factor receptor (EGFR). Moreover, CXC195 inhibited the expressions and interactions of TLR4, MyD88 and TAK1, NF-κB translocation to nucleus and its DNA binding activity, phosphorylation of ERK1/2, p38 and JNK. Our results suggested that treatment with CXC195 could attenuate the TLR4-mediated proliferation and inflammatory response in LPS-induced HepG2 cells, thus might be beneficial for the treatment of HCC.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Yiting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Thyroid Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Qunfei
authors.initials: Q
authors.lastname: Tu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Long
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Ya-Jie
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. Electronic address: liuanweinanchang@163.com.
authors.forename: Anwen
authors.initials: A
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008070:Lipopolysaccharides; D008113:Liver Neoplasms / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D010879:Piperazines; D011719:Pyrazines; D051197:Toll-Like Receptor 4; D000099151:MAP Kinase Kinase Kinase 7; C552200:CXC 195; C507779:MYD88 protein, human; C495345:TLR4 protein, human
keywords: CXC195; Hepatocellular carcinoma; Inflammation; NF-κB; Proliferation; TLR4