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Inhibition of Phosphorylated c-Jun NH(2)-terminal Kinase by 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone Isolated from Eugenia aquea Burm f. Leaves in Jurkat T-cells

BACKGROUND: Indonesian medicinal plants have been used for their anticancer activity for decades. However, the therapeutic effects of medicinal plants have not been fully examined scientifically. As cancer is a major health problem worldwide, searching for a new anticancer compound has attracted con...

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Autores principales: Barliana, Melisa I., Diantini, Ajeng, Subarnas, Anas, Abdulah, Rizky, Izumi, Takashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669100/
https://www.ncbi.nlm.nih.gov/pubmed/29142417
http://dx.doi.org/10.4103/pm.pm_16_17
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author Barliana, Melisa I.
Diantini, Ajeng
Subarnas, Anas
Abdulah, Rizky
Izumi, Takashi
author_facet Barliana, Melisa I.
Diantini, Ajeng
Subarnas, Anas
Abdulah, Rizky
Izumi, Takashi
author_sort Barliana, Melisa I.
collection PubMed
description BACKGROUND: Indonesian medicinal plants have been used for their anticancer activity for decades. However, the therapeutic effects of medicinal plants have not been fully examined scientifically. As cancer is a major health problem worldwide, searching for a new anticancer compound has attracted considerable attention. Our previous study found that 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone, an active compound isolated from leaves of Indonesian medicinal plants Eugenia aquea Burm f. (Myrtaceae), had anticancer activity in MCF-7 human breast cancer cells through induction of apoptosis. OBJECTIVE: To investigate the molecular mechanism of 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone antiproliferative activity. MATERIALS AND METHODS: Leaves of E. aquea were extracted by ethanol, fractionated by ethyl acetate, n-hexane, or water, and isolated for its active compound. Jurkat T-cells were treated with 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone for 12 and 24 h, and a cell viability assay and real-time-reverse transcriptase polymerase chain reaction for interleukin-2 (IL-2) mRNA measurement were performed. The effects of active compound to mitogen-activated protein kinases were also examined to investigate the mechanism of its antiproliferative activity. RESULTS: 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone inhibited Jurkat T-cell proliferation with a half maximal inhibitory concentration of 59.5 mM. Although IL-2 mRNA expression was slightly increased after treatment, it inhibited c-Jun N-terminal kinase expression but not p38 and extracellular signal-regulated kinase expression. CONCLUSIONS: Our study indicated that the molecular mechanism mediating the antiproliferative activity of 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone may be attributed to the stimulation of an immunological microenvironment in the cells. SUMMARY: 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone was isolated from Eugenia aquea. The antiproliferative activity of 2’,4’-dihydroxy-6- methoxy-3,5-dimethylchalcone significantly showed in Jurkat T-cells with a half maximal inhibitory concentration of 59.5 mM through inhibition of c-Jun N-terminal kinase phosphorylation. Interleukin-2 mRNA expression was also slightly increased after treatment with the compound, and this result may be indicated to the stimulation of the immunological microenvironment in T-cells. [Image: see text] Abbreviations used: E. aquea: Eugenia aquea, IL-2: Interleukin-2, MAPK: Mitogen-activated protein kinase, ERKs: Extracellular signal-regulated kinases, JNKs: c-Jun N-terminal kinases, p38: p38 MAPK, PI3K: Phosphatidylinositol-3 kinase, IC(50): Half maximal inhibitory concentration.
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spelling pubmed-56691002017-11-15 Inhibition of Phosphorylated c-Jun NH(2)-terminal Kinase by 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone Isolated from Eugenia aquea Burm f. Leaves in Jurkat T-cells Barliana, Melisa I. Diantini, Ajeng Subarnas, Anas Abdulah, Rizky Izumi, Takashi Pharmacogn Mag Original Article BACKGROUND: Indonesian medicinal plants have been used for their anticancer activity for decades. However, the therapeutic effects of medicinal plants have not been fully examined scientifically. As cancer is a major health problem worldwide, searching for a new anticancer compound has attracted considerable attention. Our previous study found that 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone, an active compound isolated from leaves of Indonesian medicinal plants Eugenia aquea Burm f. (Myrtaceae), had anticancer activity in MCF-7 human breast cancer cells through induction of apoptosis. OBJECTIVE: To investigate the molecular mechanism of 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone antiproliferative activity. MATERIALS AND METHODS: Leaves of E. aquea were extracted by ethanol, fractionated by ethyl acetate, n-hexane, or water, and isolated for its active compound. Jurkat T-cells were treated with 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone for 12 and 24 h, and a cell viability assay and real-time-reverse transcriptase polymerase chain reaction for interleukin-2 (IL-2) mRNA measurement were performed. The effects of active compound to mitogen-activated protein kinases were also examined to investigate the mechanism of its antiproliferative activity. RESULTS: 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone inhibited Jurkat T-cell proliferation with a half maximal inhibitory concentration of 59.5 mM. Although IL-2 mRNA expression was slightly increased after treatment, it inhibited c-Jun N-terminal kinase expression but not p38 and extracellular signal-regulated kinase expression. CONCLUSIONS: Our study indicated that the molecular mechanism mediating the antiproliferative activity of 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone may be attributed to the stimulation of an immunological microenvironment in the cells. SUMMARY: 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone was isolated from Eugenia aquea. The antiproliferative activity of 2’,4’-dihydroxy-6- methoxy-3,5-dimethylchalcone significantly showed in Jurkat T-cells with a half maximal inhibitory concentration of 59.5 mM through inhibition of c-Jun N-terminal kinase phosphorylation. Interleukin-2 mRNA expression was also slightly increased after treatment with the compound, and this result may be indicated to the stimulation of the immunological microenvironment in T-cells. [Image: see text] Abbreviations used: E. aquea: Eugenia aquea, IL-2: Interleukin-2, MAPK: Mitogen-activated protein kinase, ERKs: Extracellular signal-regulated kinases, JNKs: c-Jun N-terminal kinases, p38: p38 MAPK, PI3K: Phosphatidylinositol-3 kinase, IC(50): Half maximal inhibitory concentration. Medknow Publications & Media Pvt Ltd 2017-10 2017-10-11 /pmc/articles/PMC5669100/ /pubmed/29142417 http://dx.doi.org/10.4103/pm.pm_16_17 Text en Copyright: © 2017 Pharmacognosy Magazine http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Original Article
Barliana, Melisa I.
Diantini, Ajeng
Subarnas, Anas
Abdulah, Rizky
Izumi, Takashi
Inhibition of Phosphorylated c-Jun NH(2)-terminal Kinase by 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone Isolated from Eugenia aquea Burm f. Leaves in Jurkat T-cells
title Inhibition of Phosphorylated c-Jun NH(2)-terminal Kinase by 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone Isolated from Eugenia aquea Burm f. Leaves in Jurkat T-cells
title_full Inhibition of Phosphorylated c-Jun NH(2)-terminal Kinase by 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone Isolated from Eugenia aquea Burm f. Leaves in Jurkat T-cells
title_fullStr Inhibition of Phosphorylated c-Jun NH(2)-terminal Kinase by 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone Isolated from Eugenia aquea Burm f. Leaves in Jurkat T-cells
title_full_unstemmed Inhibition of Phosphorylated c-Jun NH(2)-terminal Kinase by 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone Isolated from Eugenia aquea Burm f. Leaves in Jurkat T-cells
title_short Inhibition of Phosphorylated c-Jun NH(2)-terminal Kinase by 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone Isolated from Eugenia aquea Burm f. Leaves in Jurkat T-cells
title_sort inhibition of phosphorylated c-jun nh(2)-terminal kinase by 2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone isolated from eugenia aquea burm f. leaves in jurkat t-cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669100/
https://www.ncbi.nlm.nih.gov/pubmed/29142417
http://dx.doi.org/10.4103/pm.pm_16_17
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