Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Myristoylated TMEM39AS41, a cell-permeable peptide, causes lung cancer cell death

  • Park, Sungjin (Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Kim, Minhee (Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Hong, Youngeun (Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Lee, Hyunji (Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Tran, Quangdon (Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Kim, Chaeyeong (Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Kwon, So Hee (College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University) ;
  • Park, Jisoo (Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Park, Jongsun (Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Kim, Seon-Hwan (Department of Neurosurgery, Institute for Cancer Research, College of Medicine, Chungnam National University)
  • Received : 2019.11.18
  • Accepted : 2020.01.22
  • Published : 2020.04.15
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Abstract

Lung cancer is the most common cause of cancer-associated death worldwide. Most patients with non-small cell lung cancer die within several years of the initial diagnosis, and new therapies are desperately needed. Transmembrane protein (TMEM) 39AS41, a synthetic peptide, was generated from the protein kinase B substrate motif 34GLRNRNGSAIGLPVP48 found in the human TMEM39A protein. Myristic acid was conjugated to the N-terminus of the peptide to confer cell permeability. In this study, we found that in vitro TMEM39AS41 peptide led to cell death via inhibition of inflammation/autophagy pathways in KRAS-mutated cell and tissues. In addition, TMEM39A, at a dose of 30 mg/kg, significantly suppressed tumor growth in KRASLA1 non-small cell lung cancer mice. These results suggest that the TMEM39AS41 peptide could have therapeutic potential for lung cancer.

Keywords

Acknowledgement

This work was financially supported by the research fund of Chungnam National University (Seon-Hwan Kim) and the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MEST) (NRF-2016K1A3A1A08953546, NRF-2015R1A2A2A01003597).

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