Your browser doesn't support javascript.
loading
A Novel Hydroxamate-Based Compound WMJ-J-09 Causes Head and Neck Squamous Cell Carcinoma Cell Death via LKB1-AMPK-p38MAPK-p63-Survivin Cascade.
Yen, Chia-Sheng; Choy, Cheuk-Sing; Huang, Wei-Jan; Huang, Shiu-Wen; Lai, Pin-Ye; Yu, Meng-Chieh; Shiue, Ching; Hsu, Ya-Fen; Hsu, Ming-Jen.
Afiliação
  • Yen CS; Department of General Surgery, Chi Mei Medical Center, Tainan, Taiwan.
  • Choy CS; Department of Emergency, Min-Sheng General Hospital, Taoyuan, Taiwan.
  • Huang WJ; Department of Community Medicine, En Chu Kong Hospital, New Taipei, Taiwan.
  • Huang SW; Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan.
  • Lai PY; Department of Medical Research, Taipei Medical University Hospital, Taipei, Taiwan.
  • Yu MC; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • Shiue C; Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • Hsu YF; Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • Hsu MJ; Division of General Surgery, Department of Surgery, Landseed Hospital, Taoyuan, Taiwan.
Front Pharmacol ; 9: 167, 2018.
Article em En | MEDLINE | ID: mdl-29545751
ABSTRACT
Growing evidence shows that hydroxamate-based compounds exhibit broad-spectrum pharmacological properties including anti-tumor activity. However, the precise mechanisms underlying hydroxamate derivative-induced cancer cell death remain incomplete understood. In this study, we explored the anti-tumor mechanisms of a novel aliphatic hydroxamate-based compound, WMJ-J-09, in FaDu head and neck squamous cell carcinoma (HNSCC) cells. WMJ-J-09 induced G2/M cell cycle arrest and apoptosis in FaDu cells. These actions were associated with liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38MAPK) activation, transcription factor p63 phosphorylation, as well as modulation of p21 and survivin. LKB1-AMPK-p38MAPK signaling blockade reduced WMJ-J-09's enhancing effects in p63 phosphorylation, p21 elevation and survivin reduction. Moreover, WMJ-J-09 caused an increase in α-tubulin acetylation and interfered with microtubule assembly. Furthermore, WMJ-J-09 suppressed the growth of subcutaneous FaDu xenografts in vivo. Taken together, WMJ-J-09-induced FaDu cell death may involve LKB1-AMPK-p38MAPK-p63-survivin signaling cascade. HDACs inhibition and disruption of microtubule assembly may also contribute to WMJ-J-09's actions in FaDu cells. This study suggests that WMJ-J-09 may be a potential lead compound and warrant the clinical development in the treatment of HNSCC.
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Etiology_studies Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Etiology_studies Idioma: En Ano de publicação: 2018 Tipo de documento: Article