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The cytotoxic effect and glucose uptake modulation of Baeckea frutescens on breast cancer cells

BACKGROUND: Baeckea frutescens (B. frutescens) of the family Myrtaceae is a plant that has been used in traditional medicine. It is known to have antibacterial, antipyretic and cytoprotective properties. The objective of this study is to explore the mechanism of B. frutescens leaves extracts in elim...

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Autores principales: Shahruzaman, S. H., Mustafa, M. F., Ramli, S., Maniam, S., Fakurazi, S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700976/
https://www.ncbi.nlm.nih.gov/pubmed/31426778
http://dx.doi.org/10.1186/s12906-019-2628-z
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author Shahruzaman, S. H.
Mustafa, M. F.
Ramli, S.
Maniam, S.
Fakurazi, S.
Maniam, S.
author_facet Shahruzaman, S. H.
Mustafa, M. F.
Ramli, S.
Maniam, S.
Fakurazi, S.
Maniam, S.
author_sort Shahruzaman, S. H.
collection PubMed
description BACKGROUND: Baeckea frutescens (B. frutescens) of the family Myrtaceae is a plant that has been used in traditional medicine. It is known to have antibacterial, antipyretic and cytoprotective properties. The objective of this study is to explore the mechanism of B. frutescens leaves extracts in eliminating breast cancer cells. METHOD: B. frutescens leaves extracts were prepared using Soxhlet apparatus with solvents of different polarity. The selective cytotoxicity of these extracts at various concentrations (20 to 160 μg/ml) were tested using cell viability assay after 24, 48 and 72 h of treatment. The IC(50) value in human breast cancer (MCF-7 and MDA-MB-231) and mammary breast (MCF10A) cell lines were determined. Apoptotic study using AO/PI double staining was performed using fluorescent microscope. The glucose uptake was measured using 2-NBDG, a fluorescent glucose analogue. The phytochemical screening was performed for alkaloids, flavonoids, tannins, triterpenoids, and phenols. RESULTS: B. frutescens leaves extracts showed IC(50) value ranging from 10 -127μg/ml in MCF-7 cells after 72 h of treatment. Hexane extract had the lowest IC(50) value (10μg/ml), indicating its potent selective cytotoxic activity. Morphology of MCF-7 cells after treatment with B. frutescens extracts exhibited evidence of apoptosis that included membrane blebbing and chromatin condensation. In the glucose uptake assay, B. frutescens extracts suppressed glucose uptake in cancer cells as early as 24 h upon treatment. The inhibition was significantly lower compared to the positive control WZB117 at their respective IC(50) value after 72 h incubation. It was also shown that the glucose inhibition is selective towards cancer cells compared to normal cells. The phytochemical analysis of the extract using hexane as the solvent in particular gave similar quantities of tannin, triterpenoids, flavonoid and phenols. Presumably, these metabolites have a synergistic effect in the in vitro testing, producing the potent IC(50) value and subsequently cell death. CONCLUSION: This study reports the potent selective cytotoxic effect of B. frutescens leaves hexane extract against MCF-7 cancer cells. B. frutescens extracts selectively suppressed cancer cells glucose uptake and subsequently induced cancer cell death. These findings suggest a new role of B. frutescens in cancer cell metabolism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12906-019-2628-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-67009762019-08-26 The cytotoxic effect and glucose uptake modulation of Baeckea frutescens on breast cancer cells Shahruzaman, S. H. Mustafa, M. F. Ramli, S. Maniam, S. Fakurazi, S. Maniam, S. BMC Complement Altern Med Research Article BACKGROUND: Baeckea frutescens (B. frutescens) of the family Myrtaceae is a plant that has been used in traditional medicine. It is known to have antibacterial, antipyretic and cytoprotective properties. The objective of this study is to explore the mechanism of B. frutescens leaves extracts in eliminating breast cancer cells. METHOD: B. frutescens leaves extracts were prepared using Soxhlet apparatus with solvents of different polarity. The selective cytotoxicity of these extracts at various concentrations (20 to 160 μg/ml) were tested using cell viability assay after 24, 48 and 72 h of treatment. The IC(50) value in human breast cancer (MCF-7 and MDA-MB-231) and mammary breast (MCF10A) cell lines were determined. Apoptotic study using AO/PI double staining was performed using fluorescent microscope. The glucose uptake was measured using 2-NBDG, a fluorescent glucose analogue. The phytochemical screening was performed for alkaloids, flavonoids, tannins, triterpenoids, and phenols. RESULTS: B. frutescens leaves extracts showed IC(50) value ranging from 10 -127μg/ml in MCF-7 cells after 72 h of treatment. Hexane extract had the lowest IC(50) value (10μg/ml), indicating its potent selective cytotoxic activity. Morphology of MCF-7 cells after treatment with B. frutescens extracts exhibited evidence of apoptosis that included membrane blebbing and chromatin condensation. In the glucose uptake assay, B. frutescens extracts suppressed glucose uptake in cancer cells as early as 24 h upon treatment. The inhibition was significantly lower compared to the positive control WZB117 at their respective IC(50) value after 72 h incubation. It was also shown that the glucose inhibition is selective towards cancer cells compared to normal cells. The phytochemical analysis of the extract using hexane as the solvent in particular gave similar quantities of tannin, triterpenoids, flavonoid and phenols. Presumably, these metabolites have a synergistic effect in the in vitro testing, producing the potent IC(50) value and subsequently cell death. CONCLUSION: This study reports the potent selective cytotoxic effect of B. frutescens leaves hexane extract against MCF-7 cancer cells. B. frutescens extracts selectively suppressed cancer cells glucose uptake and subsequently induced cancer cell death. These findings suggest a new role of B. frutescens in cancer cell metabolism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12906-019-2628-z) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-19 /pmc/articles/PMC6700976/ /pubmed/31426778 http://dx.doi.org/10.1186/s12906-019-2628-z Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Shahruzaman, S. H.
Mustafa, M. F.
Ramli, S.
Maniam, S.
Fakurazi, S.
Maniam, S.
The cytotoxic effect and glucose uptake modulation of Baeckea frutescens on breast cancer cells
title The cytotoxic effect and glucose uptake modulation of Baeckea frutescens on breast cancer cells
title_full The cytotoxic effect and glucose uptake modulation of Baeckea frutescens on breast cancer cells
title_fullStr The cytotoxic effect and glucose uptake modulation of Baeckea frutescens on breast cancer cells
title_full_unstemmed The cytotoxic effect and glucose uptake modulation of Baeckea frutescens on breast cancer cells
title_short The cytotoxic effect and glucose uptake modulation of Baeckea frutescens on breast cancer cells
title_sort cytotoxic effect and glucose uptake modulation of baeckea frutescens on breast cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700976/
https://www.ncbi.nlm.nih.gov/pubmed/31426778
http://dx.doi.org/10.1186/s12906-019-2628-z
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