title: Lithocholic Acid Stimulates IL-8 Expression in Human Colorectal Cancer Cells Via Activation of Erk1/2 MAPK and Suppression of STAT3 Activity.
abstract: The secondary bile acid lithocholic acid (LCA), an established tumor promoter, has been implicated in colorectal cancer (CRC) metastasis. Overexpression of interleukin-8 (IL-8) has been detected in CRC, and it contributes to poor prognosis. However, the effect of LCA on IL-8 expression is still undefined. In this study, we observed that LCA treatment induced IL-8 expression in CRC HCT116 cells. Pharmacological inhibition and mutagenesis studies indicated that Erk1/2 is critical for LCA-induced IL-8 expression. Furthermore, LCA reduced the phosphorylation of STAT3, and the STAT3 inhibitor Stattic, accelerated LCA-induced IL-8 expression, suggesting that STAT3 is involved in LCA-induced IL-8 expression. Activation of Erk1/2 functioned as an upstream signal of the STAT3 suppression induced by LCA. In conclusion, LCA activated Erk1/2 and in turn, suppressed STAT3 phosphorylation to induce IL-8 expression in HCT116 cells, thus stimulating endothelial cell proliferation and tube like formation. J. Cell. Biochem. 118: 2958-2967, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Thi Thinh
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Guangdong Province Key Laboratory of Bioship Technology, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
authors.forename: Sen
authors.initials: S
authors.lastname: Lian
authors.affiliation: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Trong Thuan
authors.initials: TT
authors.lastname: Ung
authors.affiliation: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Han
authors.affiliation: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Young Do
authors.identifier: 0000-0002-1153-5436
authors.initials: YD
authors.lastname: Jung
mesh_terms: D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008095:Lithocholic Acid / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D008095:Lithocholic Acid; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: ANGIOGENESIS; COLORECTAL CANCER; IL-8; LCA; STAT3