title: IL-6, a risk factor for hepatocellular carcinoma: FLLL32 inhibits IL-6-induced STAT3 phosphorylation in human hepatocellular cancer cells.
abstract: Hepatocellular carcinoma (HCC) is one of the most common human cancers and the patients' five-year survival rate is very low. Growing evidence indicates that interleukin-6 (IL-6) is a risk factor for HCC. High serum IL-6 may promote HCC development in hepatitis B patients. Therefore, IL-6 could be considered a HCC biomarker and blockade of IL-6 pathway may be a promising therapeutic alternative for HCC. STAT3 is major pathway to mediate signal from IL-6 to the nucleus, where different genes associated with proliferation and apoptosis are regulated. We previous reported that IL-6 induces cell survival upon drug treatment in HCC cells and inhibition of IL-6/STAT3 pathway using anti-IL-6 antibody or STAT3 small-molecule inhibitor LLL12 reduces this effect. Here we summarized the recent studies of IL-6 in HCC and showed another STAT3 small-molecule inhibitor FLLL32 also blocked IL-6-induced STAT3 activation in HCC cells. FLLL32 is a novel curcumin analogue, which has been described to suppress the constitutive activation of STAT3 in pancreatic and breast cancer cells in vitro and vivo. We demonstrated that FLLL32 blocked IL-6-induced STAT3 phosphorylation and nuclear translocation.
authors.affiliation: Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: James
authors.initials: J
authors.lastname: Fuchs
authors.forename: Chenglong
authors.initials: C
authors.lastname: Li
authors.forename: Jiayuh
authors.initials: J
authors.lastname: Lin
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D003474:Curcumin; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D000093242:Interleukin-6 Inhibitors; C548902:FLLL 32