title: 1,3,5-Trihydroxy-13,13-dimethyl-2H-pyran [7,6-b] xanthone directly targets heat shock protein 27 in hepatocellular carcinoma.
abstract: We previously showed that the small molecule 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran [7,6-b] xanthone (TDP) induces apoptosis in hepatocellular carcinoma (HCC) by suppressing Hsp27 expression, although the mechanism is not fully understood. To investigate the functional association between TDP and Hsp27 protein in HCC, recombinant Hsp27 protein was incubated with TDP at room temperature, and assayed by mass spectrum (MS) and natural electrophoresis. TDP effectively stimulated Hsp27 to form aggregates ex vitro, leading to suppression of its chaperone activity. The aggregates were degraded by the ubiquitin-proteasome (UPS) pathway. TDP directly interacted with Asp17 and Phe55 in chain C of Hsp27 on the basis of bioinformatic prediction. In conclusion, Hsp27 is a direct target of TDP in its anti-cancer activity, which provides strong support for a clinical application.
authors.affiliation: Institute Guangzhou of Advanced Technology, Chinese Academy of Sciences, Guanzhou, P.R. China; School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, P.R. China.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Fu
authors.forename: Wei-Mao
authors.initials: WM
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Zhang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D062105:Molecular Docking Simulation; D058990:Molecular Targeted Therapy; D066329:Protein Aggregates / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D044004:Xanthones / Q000494:pharmacology*
chemical_list: C576555:1,3,5-trihydroxy-13,13-dimethyl-2H-pyran(7,6-b)xanthone; D055551:HSP27 Heat-Shock Proteins; D066329:Protein Aggregates; D044004:Xanthones
keywords: 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran [7,6-b] xanthone; Autodock; Hsp27; hepatocellular carcinoma; interaction