Emetine inhibits migration and invasion of human non-small-cell lung cancer cells via regulation of ERK and p38 signaling pathways.
Emetine is a natural compound originated from ipecac roots. It was commonly used as anti-protozoal and vomiting agent. The apoptosis-inducing effect of emetine makes it considered as a potential anti-cancer agent for various human cancers. Here in this study, we report that emetine inhibits migration and invasion of human non-small-cell lung cancer (NSCLC) cells. Modulation of three major mitogen-activated protein kinases (MAPKs), ERK, p38 and JNK, is well known to be involved in regulation of matrix metalloproteinases (MMPs), which are essential in tissue remodeling and extracellular matrix (ECM) degradation, for cancer cells to spread out from the origin of tumorigenesis. Emetine regulates two major MAPKs, p38 and ERK. Differential inhibition/stimulation of ERK and p38 induced differential suppressions of β-catenin and c-myc transcription factors. This leads to the selective down-regulation of MMP-2 and MMP-9, two major gelatinases which can degrade ECM components, and RECK, a negative regulator of MMP-9.
Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Gyeonggi-Do, 461-701, South Korea.
Ji Hyun
JH
Kim
Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Gyeonggi-Do, 461-701, South Korea.
Eun Byul
EB
Cho
Department of Genetic Engineering, Sungkyunkwan University, Suwon-Si, Gyeonggi-Do, 440-746, South Korea.
Jongsung
J
Lee
Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Gyeonggi-Do, 461-701, South Korea.
Okkeun
O
Jung
Laboratory of Translational Therapeutics, Korea Research Institute of Chemical Technology, Yuseong-Gu, Daejeon, 305-600, South Korea.
Byung Jun
BJ
Ryu
Laboratory of Translational Therapeutics, Korea Research Institute of Chemical Technology, Yuseong-Gu, Daejeon, 305-600, South Korea.
Seong Hwan
SH
Kim
Department of Genetic Engineering, Sungkyunkwan University, Suwon-Si, Gyeonggi-Do, 440-746, South Korea.
Jae Youl
JY
Cho
Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-Do, 426-791, South Korea.
Chongsuk
C
Ryou
Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Gyeonggi-Do, 461-701, South Korea. Electronic address: leesaye@gachon.ac.kr.
Sang Yeol
SY
Lee
D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004640:Emetine / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D058990:Molecular Targeted Therapy; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C495270:CTNNB1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004640:Emetine
ERK; Emetine; Human non-small-cell lung cancer; Matrix metalloproteinases; Metastasis; p38