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KMID : 0379520200360020123
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한국독성학회지
2020 Volume.36 No. 2 p.123 ~ p.130
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Myristoylated TMEM39AS41, a cell-permeable peptide, causes lung cancer cell death
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Park Sung-Jin
Kim Min-Hee
Hong Young-Eun
Lee Hyun-Ji
Tran Quangdon
Kim Chae-Yeong
Kwon So-Hee
Park Ji-Soo
Park Jong-Sun
Kim Seon-Hwan
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Abstract
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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.
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KEYWORD
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Cell-penetrating peptide, Myristic acid, TMEM39A, Lung cancer, Peptide drug
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