Myristoylated TMEM39AS41, a cell-permeable peptide, causes lung cancer cell death

Sungjin Park; Minhee Kim; Youngeun Hong; Hyunji Lee; Quangdon Tran; Chaeyeong Kim; So Hee Kwon; Jisoo Park; Jongsun Park; Seon Hwan Kim

doi:10.1007/s43188-020-00038-1

Myristoylated TMEM39AS41, a cell-permeable peptide, causes lung cancer cell death

Sungjin Park, Minhee Kim, Youngeun Hong, Hyunji Lee, Quangdon Tran, Chaeyeong Kim, So Hee Kwon, Jisoo Park, Jongsun Park, Seon Hwan Kim

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

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 KRAS^LA1 non-small cell lung cancer mice. These results suggest that the TMEM39AS41 peptide could have therapeutic potential for lung cancer.

Original language	English
Pages (from-to)	123-130
Number of pages	8
Journal	Toxicological Research
Volume	36
Issue number	2
DOIs	https://doi.org/10.1007/s43188-020-00038-1
Publication status	Published - 2020 Apr 1

Bibliographical note

Funding Information:
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).

Publisher Copyright:
© 2020, Korean Society of Toxicology.

All Science Journal Classification (ASJC) codes

Toxicology
Health, Toxicology and Mutagenesis

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10.1007/s43188-020-00038-1

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title = "Myristoylated TMEM39AS41, a cell-permeable peptide, causes lung cancer cell death",

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.",

author = "Sungjin Park and Minhee Kim and Youngeun Hong and Hyunji Lee and Quangdon Tran and Chaeyeong Kim and Kwon, {So Hee} and Jisoo Park and Jongsun Park and Kim, {Seon Hwan}",

note = "Funding Information: 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). Publisher Copyright: {\textcopyright} 2020, Korean Society of Toxicology.",

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doi = "10.1007/s43188-020-00038-1",

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AU - Park, Sungjin

AU - Kim, Minhee

AU - Hong, Youngeun

AU - Lee, Hyunji

AU - Tran, Quangdon

AU - Kim, Chaeyeong

AU - Kwon, So Hee

AU - Park, Jisoo

AU - Park, Jongsun

AU - Kim, Seon Hwan

N1 - Funding Information: 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). Publisher Copyright: © 2020, Korean Society of Toxicology.

PY - 2020/4/1

Y1 - 2020/4/1

N2 - 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.

AB - 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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Myristoylated TMEM39AS41, a cell-permeable peptide, causes lung cancer cell death

Abstract

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