2. Academic Validation
  3. A Novel Small-Molecule Inhibitor Targeting CREB-CBP Complex Possesses Anti-Cancer Effects along with Cell Cycle Regulation, Autophagy Suppression and Endoplasmic Reticulum Stress

A Novel Small-Molecule Inhibitor Targeting CREB-CBP Complex Possesses Anti-Cancer Effects along with Cell Cycle Regulation, Autophagy Suppression and Endoplasmic Reticulum Stress

  • PLoS One. 2015 Apr 21;10(4):e0122628. doi: 10.1371/journal.pone.0122628.
Jong Woo Lee 1,  Hee Sun Park 1,  Sin-Aye Park 1,  Seung-Hee Ryu 2,  Wuyi Meng 3,  Juliane M Jürgensmeier 1,  Jonathan M Kurie 4,  Waun Ki Hong 4,  Julie L Boyer 1,  Roy S Herbst 5,  Ja Seok Koo 5
Affiliations

Affiliations

  • 1 Section of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, Yale University, New Haven, CT 06520, United States of America.
  • 2 Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
  • 3 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, United States of America.
  • 4 Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States of America.
  • 5 Section of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, Yale University, New Haven, CT 06520, United States of America; Translational Research Program, Yale Comprehensive Cancer Center, New Haven, CT 06520, United States of America.
PMID: 25897662 DOI: 10.1371/journal.pone.0122628
Abstract

Lung adenocarcinoma, the most common subtype of lung Cancer, is the leading cause of Cancer death worldwide. Despite attempts for the treatment of lung Cancer which have been accumulating, promising new therapies are still needed. Here, we found that cyclic-AMP response element-binding protein (CREB)-CREB binding protein (CBP) transcription factors complex inhibitor, Naphthol AS-TR phosphate (NASTRp), is a potential therapeutic agent for lung Cancer. We show that NASTRp inhibited oncogenic cell properties through cell cycle arrest with concomitant suppression of tumor-promoting Autophagy with down-regulations of Atg5-12 and Atg7, and accumulation of p62 in human lung Cancer cell lines. In addition, NASTRp induced expression of endoplasmic reticulum stress markers such as DDIT3/CHOP, and led to Apoptosis along with Bim induction. These findings suggest that transcription factor/co-activator complex, CREB-CBP, can be a potential therapeutic target and its inhibition could be a novel therapeutic strategy for lung Cancer.

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