title: HOI-02 induces apoptosis and G2-M arrest in esophageal cancer mediated by ROS.
abstract: Reactive oxygen species (ROS) are chemically reactive molecules that perform essential functions in living organisms. Accumulating evidence suggests that many types of cancer cells exhibit elevated levels of ROS. Conversely, generation of ROS has become an effective method to kill cancer cells. (E)-3-hydroxy-3-(4-(4-nitrophenyl)-2-oxobut-3-en-1-yl) indolin-2-one, which is an NO2 group-containing compound designated herein as HOI-02, generated ROS and, in a dose-dependent manner, decreased esophageal cancer cell viability and inhibited anchorage-independent growth, followed by apoptosis and G2-M arrest. Moreover, results of an in vivo study using a patient-derived xenograft mouse model showed that HOI-02 treatment suppressed the growth of esophageal tumors, without affecting the body weight of mice. The expression of Ki-67 was significantly decreased with HOI-02 treatment. In addition, the phosphorylation of c-Jun, and expression of p21, cleaved caspase 3, and DCFH-DA were increased in the HOI-02-treated group compared with the untreated control group. In contrast, treatment of cells with (E)-3-(4-(4-aminophenyl)-2-oxobut-3-en-1-yl)-3-hydroxyindolin-2-one, which is an NH2 group-containing compound designated herein as HOI-11, had no effect. Overall, we identified HOI-02 as an effective NO2 group-containing compound that was an effective therapeutic or preventive agent against esophageal cancer cell growth.
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.|Department of Pathology and Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, China.|Department of Molecular Pathology, The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.|Department of Pathology and Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, China.|Department of Molecular Pathology, The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, China.|China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
authors.forename: K
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.|China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
authors.forename: K
authors.initials: K
authors.lastname: Yao
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: K
authors.initials: K
authors.lastname: Reddy
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.|Department of Pathology and Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: G
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Zykova
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.|Program in Biomedical Informatics and Computational Biology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Shin
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ryu
authors.affiliation: Department of Pathology and Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, China.
authors.forename: Y-N
authors.initials: YN
authors.lastname: Jiang
authors.affiliation: Department of Pathology and Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: W
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: Department of Pathology and Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN, USA.|China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D016513:Mice, SCID; D008875:Middle Aged; D009578:Nitrobenzenes / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C000608413:3-hydroxy-3-(4-(4-nitrophenyl)-2-oxobut-3-en-1-yl)indolin-2-one; D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007211:Indoles; D009578:Nitrobenzenes; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; C505407:CASP3 protein, human; D053148:Caspase 3