title: Interferon-γ induces autophagy with growth inhibition and cell death in human hepatocellular carcinoma (HCC) cells through interferon-regulatory factor-1 (IRF-1).
abstract: Interferon-gamma (IFN-γ) is a pleiotropic cytokine with immunomodulatory, anti-viral, and anti-proliferative effects. In this study, we examined the effects of IFN-γ on autophagy and cell growth in human hepatocellular carcinoma (HCC) cells. IFN-γ inhibited cell growth of Huh7 cells with non-apoptotic cell death. IFN-γ induced autophagosome formation and conversion/turnover of microtubule associated protein 1 light chain 3 (LC3) protein. Furthermore, overexpression of IRF-1 also induced autophagy in Huh7 cells. Silencing IRF-1 expression with target small hairpin RNA blocked autophagy induced by IFN-γ. Silencing of the autophagy signals Beclin-1 or Atg5 attenuated the inhibitory effect of IFN-γ on Huh7 cells with decreased cell death. Additionally, IFN-γ activated autophagy in freshly cultured human HCC cells. Together, these findings show that IFN-γ induces autophagy through IRF-1 signaling pathway and the induction of autophagy contributes to the growth-inhibitory effect of IFN-γ with cell death in human liver cancer cells.
authors: Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors: Peiyuan
authors: P
authors: Li
authors: Qiang
authors: Q
authors: Du
authors: Zongxian
authors: Z
authors: Cao
authors: Zhong
authors: Z
authors: Guo
authors: John
authors: J
authors: Evankovich
authors: Wei
authors: W
authors: Yan
authors: Ying
authors: Y
authors: Chang
authors: Lifang
authors: L
authors: Shao
authors: Donna Beer
authors: DB
authors: Stolz
authors: Allan
authors: A
authors: Tsung
authors: David A
authors: DA
authors: Geller
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010588:Phagosomes / Q000187:drug effects; D015398:Signal Transduction
chemical_list: C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D007371:Interferon-gamma