title: Interferon-β-armed oncolytic adenovirus induces both apoptosis and necroptosis in cancer cells.
abstract: Interferon-β (IFN-β) has been widely used in cancer therapy, but the clinical trial results are generally disappointing. Our previous studies have shown that an oncolytic adenovirus carrying IFN-β (ZD55-IFN-β) exhibits significant anti-tumor activities. However, the underlying mechanisms are not clear. Here we showed that ZD55-IFN-β infection-induced S-phase cell cycle arrest in a p53-dependent manner by activating the ataxia telangiectasia mutated-dependent DNA damage pathway. In addition, ZD55-IFN-β infection could initiate both caspase-dependent apoptosis and necroptosis in cancer cells. More importantly, ZD55-IFN-β showed a synergistic effect on cancer cells when combined with doxorubicin. These results suggest that the combination of ZD55-IFN-β with doxorubicin may represent a promising clinical strategy in cancer therapy.
authors: State Key Laboratory of Cell Biology,  Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences,  Chinese Academy of Sciences, Shanghai 200031,  China.
authors: Hongling
authors: H
authors: Huang
authors: Tian
authors: T
authors: Xiao
authors: Lingfeng
authors: L
authors: He
authors: Hongbin
authors: H
authors: Ji
authors: Xin-Yuan
authors: XY
authors: Liu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D064007:Ataxia Telangiectasia Mutated Proteins; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D009154:Mutation; D009336:Necrosis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050504:Oncolytic Viruses / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016196:S Phase / Q000187:drug effects / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D016899:Interferon-beta; D004317:Doxorubicin; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases