<i>Mahonia aquifolium</i> Extracts Promote Doxorubicin Effects against Lung Adenocarcinoma Cells In Vitro

<i>Mahonia aquifolium</i> and its secondary metabolites have been shown to have anticancer potential. We performed MTT, scratch, and colony formation assays; analyzed cell cycle phase distribution and doxorubicin uptake and retention with flow cytometry; and detected alterations in the e...

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Main Authors: Ana Damjanović, Branka Kolundžija, Ivana Z. Matić, Ana Krivokuća, Gordana Zdunić, Katarina Šavikin, Radmila Janković, Jelena Antić Stanković, Tatjana P. Stanojković
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/22/5233
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author Ana Damjanović
Branka Kolundžija
Ivana Z. Matić
Ana Krivokuća
Gordana Zdunić
Katarina Šavikin
Radmila Janković
Jelena Antić Stanković
Tatjana P. Stanojković
author_facet Ana Damjanović
Branka Kolundžija
Ivana Z. Matić
Ana Krivokuća
Gordana Zdunić
Katarina Šavikin
Radmila Janković
Jelena Antić Stanković
Tatjana P. Stanojković
author_sort Ana Damjanović
collection DOAJ
description <i>Mahonia aquifolium</i> and its secondary metabolites have been shown to have anticancer potential. We performed MTT, scratch, and colony formation assays; analyzed cell cycle phase distribution and doxorubicin uptake and retention with flow cytometry; and detected alterations in the expression of genes involved in the formation of cell–cell interactions and migration using quantitative real-time PCR following treatment of lung adenocarcinoma cells with doxorubicin, <i>M. aquifolium</i> extracts, or their combination. MTT assay results suggested strong synergistic effects of the combined treatments, and their application led to an increase in cell numbers in the subG1 phase of the cell cycle. Both extracts were shown to prolong doxorubicin retention time in cancer cells, while the application of doxorubicin/extract combination led to a decrease in <i>MMP9</i> expression. Furthermore, cells treated with doxorubicin/extract combinations were shown to have lower migratory and colony formation potentials than untreated cells or cells treated with doxorubicin alone. The obtained results suggest that nontoxic <i>M. aquifolium</i> extracts can enhance the activity of doxorubicin, thus potentially allowing the application of lower doxorubicin doses in vivo, which may decrease its toxic effects in normal tissues.
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spelling doaj.art-74e320d701c045038ed2e384404015952023-11-20T20:25:13ZengMDPI AGMolecules1420-30492020-11-012522523310.3390/molecules25225233<i>Mahonia aquifolium</i> Extracts Promote Doxorubicin Effects against Lung Adenocarcinoma Cells In VitroAna Damjanović0Branka Kolundžija1Ivana Z. Matić2Ana Krivokuća3Gordana Zdunić4Katarina Šavikin5Radmila Janković6Jelena Antić Stanković7Tatjana P. Stanojković8Department for Experimental Oncology, Institute of Oncology and Radiology of Serbia, 11 000 Belgrade, SerbiaDepartment for Experimental Oncology, Institute of Oncology and Radiology of Serbia, 11 000 Belgrade, SerbiaDepartment for Experimental Oncology, Institute of Oncology and Radiology of Serbia, 11 000 Belgrade, SerbiaDepartment for Experimental Oncology, Institute of Oncology and Radiology of Serbia, 11 000 Belgrade, SerbiaDepartment for Pharmaceutical Investigations and Development, Institute for Medicinal Plant Research, Dr. Josif Pančić, 11 070 Belgrade, SerbiaDepartment for Pharmaceutical Investigations and Development, Institute for Medicinal Plant Research, Dr. Josif Pančić, 11 070 Belgrade, SerbiaDepartment for Experimental Oncology, Institute of Oncology and Radiology of Serbia, 11 000 Belgrade, SerbiaDepartment for Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, 11 221 Belgrade, SerbiaDepartment for Experimental Oncology, Institute of Oncology and Radiology of Serbia, 11 000 Belgrade, Serbia<i>Mahonia aquifolium</i> and its secondary metabolites have been shown to have anticancer potential. We performed MTT, scratch, and colony formation assays; analyzed cell cycle phase distribution and doxorubicin uptake and retention with flow cytometry; and detected alterations in the expression of genes involved in the formation of cell–cell interactions and migration using quantitative real-time PCR following treatment of lung adenocarcinoma cells with doxorubicin, <i>M. aquifolium</i> extracts, or their combination. MTT assay results suggested strong synergistic effects of the combined treatments, and their application led to an increase in cell numbers in the subG1 phase of the cell cycle. Both extracts were shown to prolong doxorubicin retention time in cancer cells, while the application of doxorubicin/extract combination led to a decrease in <i>MMP9</i> expression. Furthermore, cells treated with doxorubicin/extract combinations were shown to have lower migratory and colony formation potentials than untreated cells or cells treated with doxorubicin alone. The obtained results suggest that nontoxic <i>M. aquifolium</i> extracts can enhance the activity of doxorubicin, thus potentially allowing the application of lower doxorubicin doses in vivo, which may decrease its toxic effects in normal tissues.https://www.mdpi.com/1420-3049/25/22/5233doxorubicin<i>Mahonia aquifolium</i>matrix metalloproteinasescytotoxicityhuman lung adenocarcinoma
spellingShingle Ana Damjanović
Branka Kolundžija
Ivana Z. Matić
Ana Krivokuća
Gordana Zdunić
Katarina Šavikin
Radmila Janković
Jelena Antić Stanković
Tatjana P. Stanojković
<i>Mahonia aquifolium</i> Extracts Promote Doxorubicin Effects against Lung Adenocarcinoma Cells In Vitro
Molecules
doxorubicin
<i>Mahonia aquifolium</i>
matrix metalloproteinases
cytotoxicity
human lung adenocarcinoma
title <i>Mahonia aquifolium</i> Extracts Promote Doxorubicin Effects against Lung Adenocarcinoma Cells In Vitro
title_full <i>Mahonia aquifolium</i> Extracts Promote Doxorubicin Effects against Lung Adenocarcinoma Cells In Vitro
title_fullStr <i>Mahonia aquifolium</i> Extracts Promote Doxorubicin Effects against Lung Adenocarcinoma Cells In Vitro
title_full_unstemmed <i>Mahonia aquifolium</i> Extracts Promote Doxorubicin Effects against Lung Adenocarcinoma Cells In Vitro
title_short <i>Mahonia aquifolium</i> Extracts Promote Doxorubicin Effects against Lung Adenocarcinoma Cells In Vitro
title_sort i mahonia aquifolium i extracts promote doxorubicin effects against lung adenocarcinoma cells in vitro
topic doxorubicin
<i>Mahonia aquifolium</i>
matrix metalloproteinases
cytotoxicity
human lung adenocarcinoma
url https://www.mdpi.com/1420-3049/25/22/5233
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