Histone H3 lysine-trimethylation markers are decreased by recombinant methioninase and increased by methotrexate at concentrations which inhibit methionine-addicted osteosarcoma cell proliferation

Methionine addiction is a fundamental and general hallmark of cancer cells, which require exogenous methionine, despite their ability to synthesize normal amounts of methionine from homocysteine. In contrast, methionine-independent normal cells do not require exogenous methionine in the presence of...

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Autores principales:	Yusuke Aoki, Yasunori Tome, Qinghong Han, Jun Yamamoto, Kazuyuki Hamada, Noriyuki Masaki, Michael Bouvet, Kotaro Nishida, Robert M. Hoffman
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Osteosarcoma Recombinant methioninase Methionine restriction Methotrexate Methylation Histone Biology (General) QH301-705.5 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/c24b297ccc054f82a299b92b8ee866f1
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spelling	oai:doaj.org-article:c24b297ccc054f82a299b92b8ee866f12021-11-28T04:34:41ZHistone H3 lysine-trimethylation markers are decreased by recombinant methioninase and increased by methotrexate at concentrations which inhibit methionine-addicted osteosarcoma cell proliferation2405-580810.1016/j.bbrep.2021.101177https://doaj.org/article/c24b297ccc054f82a299b92b8ee866f12021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2405580821002715https://doaj.org/toc/2405-5808Methionine addiction is a fundamental and general hallmark of cancer cells, which require exogenous methionine, despite their ability to synthesize normal amounts of methionine from homocysteine. In contrast, methionine-independent normal cells do not require exogenous methionine in the presence of a methionine precursor. The methionine addiction of cancer cells is due to excess transmethylation reactions. We have previously shown that histone H3 lysine marks are over-methylated in cancer cells and the over-methylation is unstable when the cancer cells are restricted of methionine. In the present study, we show that methionine-addicted osteosarcoma cells are sensitive to both methotrexate (MTX) and recombinant methioninase (rMETase), but they affect histone H3 lysine-methylation in the opposite direction. Concentrations of MTX and rMETase, which inhibit osteosarcoma cells viability to 20%, had opposing effects on the status of histone methylation of H3K9me3 and H3K27me3. rMETase significantly decreased the amount of H3K9me3 and H3K27me3. In contrast, MTX significantly increased the amount of H3K9me and H3K27me3. The results suggest that increase or decrease in these methylated histone lysine marks is associated with proliferation arrest of methionine-addicted osteosarcoma.Yusuke AokiYasunori TomeQinghong HanJun YamamotoKazuyuki HamadaNoriyuki MasakiMichael BouvetKotaro NishidaRobert M. HoffmanElsevierarticleOsteosarcomaRecombinant methioninaseMethionine restrictionMethotrexateMethylationHistoneBiology (General)QH301-705.5BiochemistryQD415-436ENBiochemistry and Biophysics Reports, Vol 28, Iss , Pp 101177- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Osteosarcoma Recombinant methioninase Methionine restriction Methotrexate Methylation Histone Biology (General) QH301-705.5 Biochemistry QD415-436
spellingShingle	Osteosarcoma Recombinant methioninase Methionine restriction Methotrexate Methylation Histone Biology (General) QH301-705.5 Biochemistry QD415-436 Yusuke Aoki Yasunori Tome Qinghong Han Jun Yamamoto Kazuyuki Hamada Noriyuki Masaki Michael Bouvet Kotaro Nishida Robert M. Hoffman Histone H3 lysine-trimethylation markers are decreased by recombinant methioninase and increased by methotrexate at concentrations which inhibit methionine-addicted osteosarcoma cell proliferation
description	Methionine addiction is a fundamental and general hallmark of cancer cells, which require exogenous methionine, despite their ability to synthesize normal amounts of methionine from homocysteine. In contrast, methionine-independent normal cells do not require exogenous methionine in the presence of a methionine precursor. The methionine addiction of cancer cells is due to excess transmethylation reactions. We have previously shown that histone H3 lysine marks are over-methylated in cancer cells and the over-methylation is unstable when the cancer cells are restricted of methionine. In the present study, we show that methionine-addicted osteosarcoma cells are sensitive to both methotrexate (MTX) and recombinant methioninase (rMETase), but they affect histone H3 lysine-methylation in the opposite direction. Concentrations of MTX and rMETase, which inhibit osteosarcoma cells viability to 20%, had opposing effects on the status of histone methylation of H3K9me3 and H3K27me3. rMETase significantly decreased the amount of H3K9me3 and H3K27me3. In contrast, MTX significantly increased the amount of H3K9me and H3K27me3. The results suggest that increase or decrease in these methylated histone lysine marks is associated with proliferation arrest of methionine-addicted osteosarcoma.
format	article
author	Yusuke Aoki Yasunori Tome Qinghong Han Jun Yamamoto Kazuyuki Hamada Noriyuki Masaki Michael Bouvet Kotaro Nishida Robert M. Hoffman
author_facet	Yusuke Aoki Yasunori Tome Qinghong Han Jun Yamamoto Kazuyuki Hamada Noriyuki Masaki Michael Bouvet Kotaro Nishida Robert M. Hoffman
author_sort	Yusuke Aoki
title	Histone H3 lysine-trimethylation markers are decreased by recombinant methioninase and increased by methotrexate at concentrations which inhibit methionine-addicted osteosarcoma cell proliferation
title_short	Histone H3 lysine-trimethylation markers are decreased by recombinant methioninase and increased by methotrexate at concentrations which inhibit methionine-addicted osteosarcoma cell proliferation
title_full	Histone H3 lysine-trimethylation markers are decreased by recombinant methioninase and increased by methotrexate at concentrations which inhibit methionine-addicted osteosarcoma cell proliferation
title_fullStr	Histone H3 lysine-trimethylation markers are decreased by recombinant methioninase and increased by methotrexate at concentrations which inhibit methionine-addicted osteosarcoma cell proliferation
title_full_unstemmed	Histone H3 lysine-trimethylation markers are decreased by recombinant methioninase and increased by methotrexate at concentrations which inhibit methionine-addicted osteosarcoma cell proliferation
title_sort	histone h3 lysine-trimethylation markers are decreased by recombinant methioninase and increased by methotrexate at concentrations which inhibit methionine-addicted osteosarcoma cell proliferation
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/c24b297ccc054f82a299b92b8ee866f1
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Histone H3 lysine-trimethylation markers are decreased by recombinant methioninase and increased by methotrexate at concentrations which inhibit methionine-addicted osteosarcoma cell proliferation

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