title: Omentin-1, a new adipokine, promotes apoptosis through regulating Sirt1-dependent p53 deacetylation in hepatocellular carcinoma cells.
abstract: Omentin-1, a new adipokine released from adipose tissue, is associated with several key aspects of metabolic syndrome such as insulin sensitivity. However, it is not known whether omentin-1 affects cancer cell growth. In this study, we studied the influence of omentin-1 on two types of human hepatocellular carcinoma cells: HepG2 and HuH-7 cells. Cell viability assay showed that omentin-1 (1 and 2 μg/ml) significantly inhibited the proliferation of HepG2 and HuH-7 cells. Both annexin+PI staining and TUNEL assay showed that omentin-1 induced apoptosis in these cells. Moreover, omentin-1 treatment upregulated protein levels of p53 and p21, a main transcriptional target of p53. Interestingly, omentin-1 did not affect p53 mRNA level. Further mechanism study showed that omentin-1 upregulated p53 protein level through decreasing p53 deacetylation and thereby increasing the stability of p53 protein. Using small interfering RNA (siRNA)-mediated knockdown, we found that Sirt1 deacetylase, but not histone deacetylase 1 (HDAC1), was required for the effect of omentin-1 on p53 deacetylation and cancer cell proliferation. In omentin-1 treated HepG2 cells, the bax/bcl-2 protein ratio was increased, while the caspase-3 signaling pathway was also activated. Omentin-1 triggered JNK signaling but not p38 and ERK1/2 signaling pathways. Collectively, our data suggests that the novel adipokine omentin-1 may contribute to the therapeutic strategy for hepatocellular carcinoma.
authors.affiliation: Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhou
mesh_terms: D000107:Acetylation / Q000187:drug effects; D054392:Adipokines / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D058851:GPI-Linked Proteins / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D037102:Lectins / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology*; D055550:Protein Stability / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D054392:Adipokines; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016207:Cytokines; D058851:GPI-Linked Proteins; C432397:ITLN1 protein, human; D037102:Lectins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; C447939:SIRT1 protein, human; D056564:Sirtuin 1