Omentin-1, a new adipokine, promotes apoptosis through regulating Sirt1-dependent p53 deacetylation in hepatocellular carcinoma cells

• Published in: European journal of pharmacology 2013-01, Vol.698 (1-3), p.137-144
• Main Authors: Zhang, Yuan-Yuan, Zhou, Li-Ming
• Format: Article
• Language: English
• Subjects: Acetylation; Acetylation - drug effects; Adipokine; adipokines; Adipokines - pharmacology; adipose tissue; apoptosis; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Carcinoma, Hepatocellular - pathology; Caspase 3 - metabolism; cell growth; cell proliferation; Cell Proliferation - drug effects; cell viability; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Cytokines - pharmacology; Enzyme Activation - drug effects; gene expression; Gene Knockdown Techniques; GPI-Linked Proteins - pharmacology; HCC cells; Hep G2 Cells; hepatoma; histone deacetylase; human cell lines; Humans; insulin resistance; Intracellular Space - drug effects; Intracellular Space - metabolism; JNK Mitogen-Activated Protein Kinases - metabolism; Lectins - pharmacology; Liver Neoplasms - pathology; messenger RNA; metabolic syndrome; mitogen-activated protein kinase; Omentin-1; p53; pharmacology; Protein Stability - drug effects; Proto-Oncogene Proteins c-bcl-2 - metabolism; signal transduction; Signal Transduction - drug effects; Sirt1; Sirtuin 1 - deficiency; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; small interfering RNA; transcription (genetics); Tumor Suppressor Protein p53 - metabolism; Up-Regulation - drug effects
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2012.11.016

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 2μg/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.