LW1497, an Inhibitor of Malate Dehydrogenase, Suppresses TGF-β1-Induced Epithelial-Mesenchymal Transition in Lung Cancer Cells by Downregulating Slug

LW1497 suppresses the expression of the hypoxia-inducing factor (HIF)-1α inhibiting malate dehydrogenase. Although hypoxia and HIF-1α are known to be important in cancer, LW1497 has not been therapeutically applied to cancer yet. Thus, we investigated the effect of LW1497 on the epithelial-mesenchym...

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Autores principales:	Hyun Ji Kim, Mi Kyung Park, Hyun Jung Byun, Minkyoung Kim, Boram Kim, Lu Yu, Tuan Minh Nguyen, Thi Ha Nguyen, Phuong Anh Do, Eun Ji Kim, Ji Hyun Kim, Enkhmend Enkhtaivan, Kyung Sung Kim, Ji Yun Jang, Gyeoung Jin Kang, Ho Lee, Misun Won, Kyeong Lee, Jungsook Cho, Chang Hoon Lee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	malate dehydrogenase epithelial-mesenchymal transition hypoxia inducible factor-α1 slug A549 local oxygen tension Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/141c8b24db014edda9b8f8ddc25a88ea
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spelling	oai:doaj.org-article:141c8b24db014edda9b8f8ddc25a88ea2021-11-25T16:25:48ZLW1497, an Inhibitor of Malate Dehydrogenase, Suppresses TGF-β1-Induced Epithelial-Mesenchymal Transition in Lung Cancer Cells by Downregulating Slug10.3390/antiox101116742076-3921https://doaj.org/article/141c8b24db014edda9b8f8ddc25a88ea2021-10-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1674https://doaj.org/toc/2076-3921LW1497 suppresses the expression of the hypoxia-inducing factor (HIF)-1α inhibiting malate dehydrogenase. Although hypoxia and HIF-1α are known to be important in cancer, LW1497 has not been therapeutically applied to cancer yet. Thus, we investigated the effect of LW1497 on the epithelial-mesenchymal transition (EMT) of lung cancer cells. A549 and H1299 lung cancer cells were induced to undergo via TGF-β1 treatment, resulting in the downregulation of E-cadherin and upregulation of N-cadherin and Vimentin concurrently with increases in the migration and invasion capacities of the cells. These effects of TGF-β1 were suppressed upon co-treatment of the cells with LW1497. An RNA-seq analysis revealed that LW1497 induced differential expression of genes related to hypoxia, RNA splicing, angiogenesis, cell migration, and metastasis in the A549 lung cancer cell lines. We confirmed the differential expression of Slug, an EMT-related transcription factor. Results from Western blotting and RT-PCR confirmed that LW1497 inhibited the expression of EMT markers and Slug. After orthotopically transplanting A549 cancer cells into mice, LW1497 was administered to examine whether the lung cancer progression was inhibited. We observed that LW1497 reduced the area of cancer. In addition, the results from immunohistochemical analyses showed that LW1497 downregulated EMT markers and Slug. In conclusion, LW1497 suppresses cancer progression through the inhibition of EMT by downregulating Slug.Hyun Ji KimMi Kyung ParkHyun Jung ByunMinkyoung KimBoram KimLu YuTuan Minh NguyenThi Ha NguyenPhuong Anh DoEun Ji KimJi Hyun KimEnkhmend EnkhtaivanKyung Sung KimJi Yun JangGyeoung Jin KangHo LeeMisun WonKyeong LeeJungsook ChoChang Hoon LeeMDPI AGarticlemalate dehydrogenaseepithelial-mesenchymal transitionhypoxia inducible factor-α1slugA549local oxygen tensionTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1674, p 1674 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	malate dehydrogenase epithelial-mesenchymal transition hypoxia inducible factor-α1 slug A549 local oxygen tension Therapeutics. Pharmacology RM1-950
spellingShingle	malate dehydrogenase epithelial-mesenchymal transition hypoxia inducible factor-α1 slug A549 local oxygen tension Therapeutics. Pharmacology RM1-950 Hyun Ji Kim Mi Kyung Park Hyun Jung Byun Minkyoung Kim Boram Kim Lu Yu Tuan Minh Nguyen Thi Ha Nguyen Phuong Anh Do Eun Ji Kim Ji Hyun Kim Enkhmend Enkhtaivan Kyung Sung Kim Ji Yun Jang Gyeoung Jin Kang Ho Lee Misun Won Kyeong Lee Jungsook Cho Chang Hoon Lee LW1497, an Inhibitor of Malate Dehydrogenase, Suppresses TGF-β1-Induced Epithelial-Mesenchymal Transition in Lung Cancer Cells by Downregulating Slug
description	LW1497 suppresses the expression of the hypoxia-inducing factor (HIF)-1α inhibiting malate dehydrogenase. Although hypoxia and HIF-1α are known to be important in cancer, LW1497 has not been therapeutically applied to cancer yet. Thus, we investigated the effect of LW1497 on the epithelial-mesenchymal transition (EMT) of lung cancer cells. A549 and H1299 lung cancer cells were induced to undergo via TGF-β1 treatment, resulting in the downregulation of E-cadherin and upregulation of N-cadherin and Vimentin concurrently with increases in the migration and invasion capacities of the cells. These effects of TGF-β1 were suppressed upon co-treatment of the cells with LW1497. An RNA-seq analysis revealed that LW1497 induced differential expression of genes related to hypoxia, RNA splicing, angiogenesis, cell migration, and metastasis in the A549 lung cancer cell lines. We confirmed the differential expression of Slug, an EMT-related transcription factor. Results from Western blotting and RT-PCR confirmed that LW1497 inhibited the expression of EMT markers and Slug. After orthotopically transplanting A549 cancer cells into mice, LW1497 was administered to examine whether the lung cancer progression was inhibited. We observed that LW1497 reduced the area of cancer. In addition, the results from immunohistochemical analyses showed that LW1497 downregulated EMT markers and Slug. In conclusion, LW1497 suppresses cancer progression through the inhibition of EMT by downregulating Slug.
format	article
author	Hyun Ji Kim Mi Kyung Park Hyun Jung Byun Minkyoung Kim Boram Kim Lu Yu Tuan Minh Nguyen Thi Ha Nguyen Phuong Anh Do Eun Ji Kim Ji Hyun Kim Enkhmend Enkhtaivan Kyung Sung Kim Ji Yun Jang Gyeoung Jin Kang Ho Lee Misun Won Kyeong Lee Jungsook Cho Chang Hoon Lee
author_facet	Hyun Ji Kim Mi Kyung Park Hyun Jung Byun Minkyoung Kim Boram Kim Lu Yu Tuan Minh Nguyen Thi Ha Nguyen Phuong Anh Do Eun Ji Kim Ji Hyun Kim Enkhmend Enkhtaivan Kyung Sung Kim Ji Yun Jang Gyeoung Jin Kang Ho Lee Misun Won Kyeong Lee Jungsook Cho Chang Hoon Lee
author_sort	Hyun Ji Kim
title	LW1497, an Inhibitor of Malate Dehydrogenase, Suppresses TGF-β1-Induced Epithelial-Mesenchymal Transition in Lung Cancer Cells by Downregulating Slug
title_short	LW1497, an Inhibitor of Malate Dehydrogenase, Suppresses TGF-β1-Induced Epithelial-Mesenchymal Transition in Lung Cancer Cells by Downregulating Slug
title_full	LW1497, an Inhibitor of Malate Dehydrogenase, Suppresses TGF-β1-Induced Epithelial-Mesenchymal Transition in Lung Cancer Cells by Downregulating Slug
title_fullStr	LW1497, an Inhibitor of Malate Dehydrogenase, Suppresses TGF-β1-Induced Epithelial-Mesenchymal Transition in Lung Cancer Cells by Downregulating Slug
title_full_unstemmed	LW1497, an Inhibitor of Malate Dehydrogenase, Suppresses TGF-β1-Induced Epithelial-Mesenchymal Transition in Lung Cancer Cells by Downregulating Slug
title_sort	lw1497, an inhibitor of malate dehydrogenase, suppresses tgf-β1-induced epithelial-mesenchymal transition in lung cancer cells by downregulating slug
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/141c8b24db014edda9b8f8ddc25a88ea
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LW1497, an Inhibitor of Malate Dehydrogenase, Suppresses TGF-β1-Induced Epithelial-Mesenchymal Transition in Lung Cancer Cells by Downregulating Slug

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