RRC ID 34744
Author Maeda S, Wada H, Naito Y, Nagano H, Simmons S, Kagawa Y, Naito A, Kikuta J, Ishii T, Tomimaru Y, Hama N, Kawamoto K, Kobayashi S, Eguchi H, Umeshita K, Ishii H, Doki Y, Mori M, Ishii M.
Title Interferon-α acts on the S/G2/M phases to induce apoptosis in the G1 phase of an IFNAR2-expressing hepatocellular carcinoma cell line.
Journal J. Biol. Chem.
Abstract Interferon-α (IFN-α) is used clinically to treat hepatocellular carcinoma (HCC), although the detailed therapeutic mechanisms remain elusive. In particular, IFN-α has long been implicated in control of the cell cycle, but its actual point of action has not been clarified. Here, using time lapse imaging analyses of the human HCC cell line HuH7 carrying a fluorescence ubiquitination-based cell cycle indicator (Fucci), we found that IFN-α induced cell cycle arrest in the G0/G1 phases, leading to apoptosis through an IFN-α type-2 receptor (IFNAR2)-dependent signaling pathway. Detailed analyses by time lapse imaging and biochemical assays demonstrated that the IFN-α/IFNAR2 axis sensitizes cells to apoptosis in the S/G2/M phases in preparation for cell death in the G0/G1 phases. In summary, this study is the first to demonstrate the detailed mechanism of IFN-α as an anticancer drug, using Fucci-based time lapse imaging, which will be informative for treating HCC with IFN-α in clinical practice.
Volume 289(34)
Pages 23786-95
Published 2014-8-22
DOI 10.1074/jbc.M114.551879
PII M114.551879
PMID 25012666
PMC PMC4156060
MeSH Blotting, Western Carcinoma, Hepatocellular / metabolism Carcinoma, Hepatocellular / pathology* Cell Cycle / drug effects* Cell Line, Tumor DNA Primers Flow Cytometry Humans Interferon-alpha / pharmacology* Liver Neoplasms / metabolism Liver Neoplasms / pathology* Real-Time Polymerase Chain Reaction Receptor, Interferon alpha-beta / metabolism*
IF 4.011
Times Cited 8
DNA material CSII-EF-MCS (RDB04378)