Mustard Seed (<i>Brassica nigra</i>) Extract Exhibits Antiproliferative Effect against Human Lung Cancer Cells through Differential Regulation of Apoptosis, Cell Cycle, Migration, and Invasion

Lung cancer is the primary cause of cancer-related death worldwide, and development of novel lung cancer preventive and therapeutic agents are urgently needed. <i>Brassica nigra</i> (black mustard) seeds are commonly consumed in several Asian and African countries. Mustard seeds previous...

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Main Authors: Asmaa Gamal Ahmed, Usama Khamis Hussein, Amr E. Ahmed, Kyoung Min Kim, Hamada M. Mahmoud, Ola Hammouda, Kyu Yun Jang, Anupam Bishayee
Format: Article
Language:English
Published: MDPI AG 2020-04-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/9/2069
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author Asmaa Gamal Ahmed
Usama Khamis Hussein
Amr E. Ahmed
Kyoung Min Kim
Hamada M. Mahmoud
Ola Hammouda
Kyu Yun Jang
Anupam Bishayee
author_facet Asmaa Gamal Ahmed
Usama Khamis Hussein
Amr E. Ahmed
Kyoung Min Kim
Hamada M. Mahmoud
Ola Hammouda
Kyu Yun Jang
Anupam Bishayee
author_sort Asmaa Gamal Ahmed
collection DOAJ
description Lung cancer is the primary cause of cancer-related death worldwide, and development of novel lung cancer preventive and therapeutic agents are urgently needed. <i>Brassica nigra</i> (black mustard) seeds are commonly consumed in several Asian and African countries. Mustard seeds previously exhibited significant anticancer activities against several cancer types. In the present study, we have investigated various cellular and molecular mechanisms of anticancer effects of an ethanolic extract of <i>B. nigra</i> seeds against A549 and H1299 human non-small cell lung cancer cell lines. <i>B. nigra</i> extract showed a substantial growth-inhibitory effect as it reduced the viability and clonogenic survival of A549 and H1299 cells in a concentration-dependent manner. <i>B. nigra</i> extract induced cellular apoptosis in a time- and concentration-dependent fashion as evidenced from increased caspase-3 activity. Furthermore, treatment of both A549 and H1299 cells with <i>B. nigra</i> extract alone or in combination with camptothecin induced DNA double-strand breaks as evidenced by upregulation of γH2A histone family member X, Fanconi anemia group D2 protein, Fanconi anemia group J protein, ataxia-telangiectesia mutated and Rad3-related protein. Based on cell cycle analysis, <i>B. nigra</i> extract significantly arrested A549 and H1299 cells at S and G2/M phases. Additionally, <i>B. nigra</i> extract suppressed the migratory and invasive properties of both cell lines, downregulated the expression of matrix metalloproteinase-2 (MMP2), MMP9, and Snail and upregulated the expression of E-cadherin at mRNA and protein levels. Taken together, these findings indicate that <i>B. nigra</i> seed extract may have an important anticancer potential against human lung cancer which could be mediated through simultaneous and differential regulation of proliferation, apoptosis, DNA damage, cell cycle, migration, and invasion.
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spelling doaj.art-f34f7394c9384c06b56f731555cdeb082023-11-19T23:00:43ZengMDPI AGMolecules1420-30492020-04-01259206910.3390/molecules25092069Mustard Seed (<i>Brassica nigra</i>) Extract Exhibits Antiproliferative Effect against Human Lung Cancer Cells through Differential Regulation of Apoptosis, Cell Cycle, Migration, and InvasionAsmaa Gamal Ahmed0Usama Khamis Hussein1Amr E. Ahmed2Kyoung Min Kim3Hamada M. Mahmoud4Ola Hammouda5Kyu Yun Jang6Anupam Bishayee7Department of Pathology, Chonbuk National University Medical School, Jeonju 54907, KoreaDepartment of Pathology, Chonbuk National University Medical School, Jeonju 54907, KoreaDepartment of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef 62511, EgyptDepartment of Pathology, Chonbuk National University Medical School, Jeonju 54907, KoreaFaculty of Science, Beni-Suef University, Beni-Suef 62511, EgyptFaculty of Science, Beni-Suef University, Beni-Suef 62511, EgyptDepartment of Pathology, Chonbuk National University Medical School, Jeonju 54907, KoreaLake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USALung cancer is the primary cause of cancer-related death worldwide, and development of novel lung cancer preventive and therapeutic agents are urgently needed. <i>Brassica nigra</i> (black mustard) seeds are commonly consumed in several Asian and African countries. Mustard seeds previously exhibited significant anticancer activities against several cancer types. In the present study, we have investigated various cellular and molecular mechanisms of anticancer effects of an ethanolic extract of <i>B. nigra</i> seeds against A549 and H1299 human non-small cell lung cancer cell lines. <i>B. nigra</i> extract showed a substantial growth-inhibitory effect as it reduced the viability and clonogenic survival of A549 and H1299 cells in a concentration-dependent manner. <i>B. nigra</i> extract induced cellular apoptosis in a time- and concentration-dependent fashion as evidenced from increased caspase-3 activity. Furthermore, treatment of both A549 and H1299 cells with <i>B. nigra</i> extract alone or in combination with camptothecin induced DNA double-strand breaks as evidenced by upregulation of γH2A histone family member X, Fanconi anemia group D2 protein, Fanconi anemia group J protein, ataxia-telangiectesia mutated and Rad3-related protein. Based on cell cycle analysis, <i>B. nigra</i> extract significantly arrested A549 and H1299 cells at S and G2/M phases. Additionally, <i>B. nigra</i> extract suppressed the migratory and invasive properties of both cell lines, downregulated the expression of matrix metalloproteinase-2 (MMP2), MMP9, and Snail and upregulated the expression of E-cadherin at mRNA and protein levels. Taken together, these findings indicate that <i>B. nigra</i> seed extract may have an important anticancer potential against human lung cancer which could be mediated through simultaneous and differential regulation of proliferation, apoptosis, DNA damage, cell cycle, migration, and invasion.https://www.mdpi.com/1420-3049/25/9/2069<i>Brassica nigra</i>lung cancerproliferationDNA damageapoptosis
spellingShingle Asmaa Gamal Ahmed
Usama Khamis Hussein
Amr E. Ahmed
Kyoung Min Kim
Hamada M. Mahmoud
Ola Hammouda
Kyu Yun Jang
Anupam Bishayee
Mustard Seed (<i>Brassica nigra</i>) Extract Exhibits Antiproliferative Effect against Human Lung Cancer Cells through Differential Regulation of Apoptosis, Cell Cycle, Migration, and Invasion
Molecules
<i>Brassica nigra</i>
lung cancer
proliferation
DNA damage
apoptosis
title Mustard Seed (<i>Brassica nigra</i>) Extract Exhibits Antiproliferative Effect against Human Lung Cancer Cells through Differential Regulation of Apoptosis, Cell Cycle, Migration, and Invasion
title_full Mustard Seed (<i>Brassica nigra</i>) Extract Exhibits Antiproliferative Effect against Human Lung Cancer Cells through Differential Regulation of Apoptosis, Cell Cycle, Migration, and Invasion
title_fullStr Mustard Seed (<i>Brassica nigra</i>) Extract Exhibits Antiproliferative Effect against Human Lung Cancer Cells through Differential Regulation of Apoptosis, Cell Cycle, Migration, and Invasion
title_full_unstemmed Mustard Seed (<i>Brassica nigra</i>) Extract Exhibits Antiproliferative Effect against Human Lung Cancer Cells through Differential Regulation of Apoptosis, Cell Cycle, Migration, and Invasion
title_short Mustard Seed (<i>Brassica nigra</i>) Extract Exhibits Antiproliferative Effect against Human Lung Cancer Cells through Differential Regulation of Apoptosis, Cell Cycle, Migration, and Invasion
title_sort mustard seed i brassica nigra i extract exhibits antiproliferative effect against human lung cancer cells through differential regulation of apoptosis cell cycle migration and invasion
topic <i>Brassica nigra</i>
lung cancer
proliferation
DNA damage
apoptosis
url https://www.mdpi.com/1420-3049/25/9/2069
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