title: Suppression of autophagy enhanced growth inhibition and apoptosis of interferon-β in human glioma cells.
abstract: Interferon-beta (IFN-β) is a cytokine with anti-viral, anti-proliferative, and immunomodulatory effects. In this study, we investigated the effects of IFN-β on the induction of autophagy and the relationships among autophagy, growth inhibition, and apoptosis induced by IFN-β in human glioma cells. We found that IFN-β induced autophagosome formation and conversion of microtubule associated protein 1 light chain 3 (LC3) protein, whereas it inhibited cell growth through caspase-dependent cell apoptosis. The Akt/mTOR signaling pathway was involved in autophagy induced by IFN-β. A dose- and time-dependent increase of p-ERK 1/2 expression was also observed in human glioma cells treated with IFN-β. Autophagy induced by IFN-β was suppressed when p-ERK1/2 was impaired by treatment with U0126. We also demonstrated that suppression of autophagy significantly enhanced growth inhibition and cell apoptosis induced by IFN-β, whereas inhibition of caspase-dependent cell apoptosis impaired autophagy induced by IFN-β. Collectively, these findings indicated that autophagy induced by IFN-β was associated with the Akt/mTOR and ERK 1/2 signaling pathways, and inhibition of autophagy could enhance the growth inhibitory effects of IFN-β and increase apoptosis in human glioma cells. Together, these findings support the possibility that autophagy inhibitors may improve IFN-β therapy for gliomas.
authors: Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors: Yubin
authors: Y
authors: Li
authors: Haiyan
authors: H
authors: Zhu
authors: Xian
authors: X
authors: Zeng
authors: Jiajun
authors: J
authors: Fan
authors: Xiaolu
authors: X
authors: Qian
authors: Shaofei
authors: S
authors: Wang
authors: Ziyu
authors: Z
authors: Wang
authors: Yun
authors: Y
authors: Sun
authors: Xiaodan
authors: X
authors: Wang
authors: Weiwu
authors: W
authors: Wang
authors: Dianwen
authors: D
authors: Ju
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005910:Glioma / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D016899:Interferon-beta; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases