Harmine Hydrochloride Mediates the Induction of G2/M Cell Cycle Arrest in Breast Cancer Cells by Regulating the MAPKs and AKT/FOXO3a Signaling Pathways

Breast cancer (BC) is one of the most common causes of death among women worldwide. Recently, interest in novel approaches for BC has increased by developing new drugs derived from natural products with reduced side effects. This study aimed to treat BC cells with harmine hydrochloride (HMH) to iden...

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Autores principales:	Chae Won Ock, Gi Dae Kim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	harmine hydrochloride G2/M cell cycle arrest AKT/FOXO3a Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/f3a434a6b8eb41dc817006ecfaf8d804
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spelling	oai:doaj.org-article:f3a434a6b8eb41dc817006ecfaf8d8042021-11-11T18:39:28ZHarmine Hydrochloride Mediates the Induction of G2/M Cell Cycle Arrest in Breast Cancer Cells by Regulating the MAPKs and AKT/FOXO3a Signaling Pathways10.3390/molecules262167141420-3049https://doaj.org/article/f3a434a6b8eb41dc817006ecfaf8d8042021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6714https://doaj.org/toc/1420-3049Breast cancer (BC) is one of the most common causes of death among women worldwide. Recently, interest in novel approaches for BC has increased by developing new drugs derived from natural products with reduced side effects. This study aimed to treat BC cells with harmine hydrochloride (HMH) to identify its anticancer effects and mechanisms. HMH treatment suppressed cell growth, migration, invasion, and colony formation in MCF-7 and MDA-MB-231 cells, regardless of the hormone signaling. It also reduced the phosphorylation of PI3K, AKT, and mTOR and increased FOXO3a expression. Additionally, HMH treatment increased p38 phosphorylation in MCF-7 cells and activated c-Jun N-terminal kinase (JNK) phosphorylation in MDA-MB-231 cells in a dose-dependent manner, where activated p38 and JNK increased FOXO3a expression. Activated FOXO3a increased the expression of p53, p21, and their downstream proteins, including p-cdc25, p-cdc2, and cyclin B1, to induce G2/M cell cycle arrest. Furthermore, HMH inhibited the PI3K/AKT/mTOR pathway by significantly reducing p-AKT expression in combination with LY294002, an AKT inhibitor. These results indicate that mitogen-activated protein kinases (MAPKs) and AKT/FOXO3a signaling pathways mediate the induction of cell cycle arrest following HMH treatment. Therefore, HMH could be a potential active compound for anticancer bioactivity in BC cells.Chae Won OckGi Dae KimMDPI AGarticleharmine hydrochlorideG2/M cell cycle arrestAKT/FOXO3aOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6714, p 6714 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	harmine hydrochloride G2/M cell cycle arrest AKT/FOXO3a Organic chemistry QD241-441
spellingShingle	harmine hydrochloride G2/M cell cycle arrest AKT/FOXO3a Organic chemistry QD241-441 Chae Won Ock Gi Dae Kim Harmine Hydrochloride Mediates the Induction of G2/M Cell Cycle Arrest in Breast Cancer Cells by Regulating the MAPKs and AKT/FOXO3a Signaling Pathways
description	Breast cancer (BC) is one of the most common causes of death among women worldwide. Recently, interest in novel approaches for BC has increased by developing new drugs derived from natural products with reduced side effects. This study aimed to treat BC cells with harmine hydrochloride (HMH) to identify its anticancer effects and mechanisms. HMH treatment suppressed cell growth, migration, invasion, and colony formation in MCF-7 and MDA-MB-231 cells, regardless of the hormone signaling. It also reduced the phosphorylation of PI3K, AKT, and mTOR and increased FOXO3a expression. Additionally, HMH treatment increased p38 phosphorylation in MCF-7 cells and activated c-Jun N-terminal kinase (JNK) phosphorylation in MDA-MB-231 cells in a dose-dependent manner, where activated p38 and JNK increased FOXO3a expression. Activated FOXO3a increased the expression of p53, p21, and their downstream proteins, including p-cdc25, p-cdc2, and cyclin B1, to induce G2/M cell cycle arrest. Furthermore, HMH inhibited the PI3K/AKT/mTOR pathway by significantly reducing p-AKT expression in combination with LY294002, an AKT inhibitor. These results indicate that mitogen-activated protein kinases (MAPKs) and AKT/FOXO3a signaling pathways mediate the induction of cell cycle arrest following HMH treatment. Therefore, HMH could be a potential active compound for anticancer bioactivity in BC cells.
format	article
author	Chae Won Ock Gi Dae Kim
author_facet	Chae Won Ock Gi Dae Kim
author_sort	Chae Won Ock
title	Harmine Hydrochloride Mediates the Induction of G2/M Cell Cycle Arrest in Breast Cancer Cells by Regulating the MAPKs and AKT/FOXO3a Signaling Pathways
title_short	Harmine Hydrochloride Mediates the Induction of G2/M Cell Cycle Arrest in Breast Cancer Cells by Regulating the MAPKs and AKT/FOXO3a Signaling Pathways
title_full	Harmine Hydrochloride Mediates the Induction of G2/M Cell Cycle Arrest in Breast Cancer Cells by Regulating the MAPKs and AKT/FOXO3a Signaling Pathways
title_fullStr	Harmine Hydrochloride Mediates the Induction of G2/M Cell Cycle Arrest in Breast Cancer Cells by Regulating the MAPKs and AKT/FOXO3a Signaling Pathways
title_full_unstemmed	Harmine Hydrochloride Mediates the Induction of G2/M Cell Cycle Arrest in Breast Cancer Cells by Regulating the MAPKs and AKT/FOXO3a Signaling Pathways
title_sort	harmine hydrochloride mediates the induction of g2/m cell cycle arrest in breast cancer cells by regulating the mapks and akt/foxo3a signaling pathways
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f3a434a6b8eb41dc817006ecfaf8d804
work_keys_str_mv	AT chaewonock harminehydrochloridemediatestheinductionofg2mcellcyclearrestinbreastcancercellsbyregulatingthemapksandaktfoxo3asignalingpathways AT gidaekim harminehydrochloridemediatestheinductionofg2mcellcyclearrestinbreastcancercellsbyregulatingthemapksandaktfoxo3asignalingpathways
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Harmine Hydrochloride Mediates the Induction of G2/M Cell Cycle Arrest in Breast Cancer Cells by Regulating the MAPKs and AKT/FOXO3a Signaling Pathways

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