Your browser doesn't support javascript.
loading
2-anilino-4-amino-5-aroylthiazole-type compound AS7128 inhibits lung cancer growth through decreased iASPP and p53 interaction.
Cheng, Hao-Wei; Chein, Rong-Jie; Cheng, Ting-Jen; Wu, Pei-Shan; Wu, Hsin-Yi; Hung, Pei-Fang; Wang, Chia-Jen; Hsu, Yuan-Ling; Wong, Jau-Min; Yuan, Ang; Wong, Chi-Huey; Yang, Pan-Chyr; Pan, Szu-Hua.
Afiliação
  • Cheng HW; Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
  • Chein RJ; Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
  • Cheng TJ; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Wu PS; Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei, Taiwan.
  • Wu HY; Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
  • Hung PF; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • Wang CJ; Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  • Hsu YL; Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan.
  • Wong JM; Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
  • Yuan A; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • Wong CH; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • Yang PC; Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • Pan SH; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Cancer Sci ; 109(3): 832-842, 2018 Mar.
Article em En | MEDLINE | ID: mdl-29285847
Lung cancer is the leading cause of cancer-related death worldwide. Thus, developing novel therapeutic agents has become critical for lung cancer treatment. In this study, compound AS7128 was selected from a 2-million entry chemical library screening and identified as a candidate drug against non-small cell lung cancer in vitro and in vivo. Further investigation indicated that AS7128 could induce cell apoptosis and cell cycle arrest, especially in the mitosis stage. In addition, we also found that iASPP, an oncogenic protein that functionally inhibits p53, might be associated with AS7128 through mass identification. Further exploration indicated that AS7128 treatment could restore the transactivation ability of p53 and, thus, increase the expressions of its downstream target genes, which are related to cell cycle arrest and apoptosis. This occurs through disruption of the interactions between p53 and iASPP in cells. Taken together, AS7128 could bind to iASPP, disrupt the interaction between iASPP and p53, and result in cell cycle arrest and apoptosis. These findings may provide new insight for using iASPP as a therapeutic target for non-small cell lung cancer treatment.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Tiazóis / Proteína Supressora de Tumor p53 / Carcinoma Pulmonar de Células não Pequenas / Peptídeos e Proteínas de Sinalização Intracelular / Neoplasias Pulmonares / Antineoplásicos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Tiazóis / Proteína Supressora de Tumor p53 / Carcinoma Pulmonar de Células não Pequenas / Peptídeos e Proteínas de Sinalização Intracelular / Neoplasias Pulmonares / Antineoplásicos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article