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The apoptotic effects of Brucea javanica fruit extract against HT29 cells associated with p53 upregulation and inhibition of NF-κB translocation

BACKGROUND: Brucea javanica (L.) Merr. is a plant from the genus Brucea, which is used in local traditional medicine to treat various diseases. Recent studies revealed an impressive anticancer efficiency of B. javanica extract in different types of cancer cells. PURPOSE: In this study, we have inves...

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Autores principales: Bagheri, Elham, Hajiaghaalipour, Fatemeh, Nyamathulla, Shaik, Salehen, Nur’Ain
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881282/
https://www.ncbi.nlm.nih.gov/pubmed/29636600
http://dx.doi.org/10.2147/DDDT.S155115
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author Bagheri, Elham
Hajiaghaalipour, Fatemeh
Nyamathulla, Shaik
Salehen, Nur’Ain
author_facet Bagheri, Elham
Hajiaghaalipour, Fatemeh
Nyamathulla, Shaik
Salehen, Nur’Ain
author_sort Bagheri, Elham
collection PubMed
description BACKGROUND: Brucea javanica (L.) Merr. is a plant from the genus Brucea, which is used in local traditional medicine to treat various diseases. Recent studies revealed an impressive anticancer efficiency of B. javanica extract in different types of cancer cells. PURPOSE: In this study, we have investigated the cytotoxic effects of the B. javanica hexane, ethanolic extracts against colon cancer cells. HT29 colon cells were selected as an in vitro cancer model to evaluate the anticancer activity of B. javanica ethanolic extract (BJEE) and the possible mechanisms of action that induced apoptosis. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2, 5,-diphenyltetrazolium bromide (MTT), lactate dehydrogenase, acridine orange/propidium iodide, and annexin-V-fluorescein isothiocyanate assays were performed to determine the antiproliferative and apoptosis validation of BJEE on cancer cells. Measurement of reactive oxygen species (ROS) production, caspase activities, nucleus factor-κB activity, and gene expression experiments was done to investigate the potential mechanisms of action in the apoptotic process. RESULTS: The results obtained from this study illustrated the significant antiproliferative effect of BJEE on colorectal cancer cells, with a concentration value that inhibits 50% of the cell growth of 25±3.1 µg/mL after 72 h of treatment. MTT assay demonstrated that the BJEE is selectively toxic to cancer cells, and BJEE induced cell apoptosis via activation of caspase-8 along with modulation of apoptosis-related proteins such as Fas, CD40, tumor necrosis factor-related apoptosis-inducing ligands, and tumor necrosis factor receptors, which confirmed the contribution of extrinsic pathway. Meanwhile, increased ROS production in treated cells subsequently activated caspase-9 production, which triggered the intrinsic pathways. In addition, overexpression of cytochrome-c, Bax, and Bad proteins along with suppression of Bcl-2 illustrated that mitochondrial-dependent pathway also contributed to BJEE-induced cell death. Consistent with the findings from this study, BJEE-induced cancer cell death proceeds via extrinsic and intrinsic mitochondrial-dependent and -independent events. CONCLUSION: From the evidence obtained from this study, it is concluded that the BJEE is a promising natural extract to combat colorectal cancer cells (HT29 cells) via induction of apoptosis through activation of extrinsic and intrinsic pathways.
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spelling pubmed-58812822018-04-10 The apoptotic effects of Brucea javanica fruit extract against HT29 cells associated with p53 upregulation and inhibition of NF-κB translocation Bagheri, Elham Hajiaghaalipour, Fatemeh Nyamathulla, Shaik Salehen, Nur’Ain Drug Des Devel Ther Original Research BACKGROUND: Brucea javanica (L.) Merr. is a plant from the genus Brucea, which is used in local traditional medicine to treat various diseases. Recent studies revealed an impressive anticancer efficiency of B. javanica extract in different types of cancer cells. PURPOSE: In this study, we have investigated the cytotoxic effects of the B. javanica hexane, ethanolic extracts against colon cancer cells. HT29 colon cells were selected as an in vitro cancer model to evaluate the anticancer activity of B. javanica ethanolic extract (BJEE) and the possible mechanisms of action that induced apoptosis. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2, 5,-diphenyltetrazolium bromide (MTT), lactate dehydrogenase, acridine orange/propidium iodide, and annexin-V-fluorescein isothiocyanate assays were performed to determine the antiproliferative and apoptosis validation of BJEE on cancer cells. Measurement of reactive oxygen species (ROS) production, caspase activities, nucleus factor-κB activity, and gene expression experiments was done to investigate the potential mechanisms of action in the apoptotic process. RESULTS: The results obtained from this study illustrated the significant antiproliferative effect of BJEE on colorectal cancer cells, with a concentration value that inhibits 50% of the cell growth of 25±3.1 µg/mL after 72 h of treatment. MTT assay demonstrated that the BJEE is selectively toxic to cancer cells, and BJEE induced cell apoptosis via activation of caspase-8 along with modulation of apoptosis-related proteins such as Fas, CD40, tumor necrosis factor-related apoptosis-inducing ligands, and tumor necrosis factor receptors, which confirmed the contribution of extrinsic pathway. Meanwhile, increased ROS production in treated cells subsequently activated caspase-9 production, which triggered the intrinsic pathways. In addition, overexpression of cytochrome-c, Bax, and Bad proteins along with suppression of Bcl-2 illustrated that mitochondrial-dependent pathway also contributed to BJEE-induced cell death. Consistent with the findings from this study, BJEE-induced cancer cell death proceeds via extrinsic and intrinsic mitochondrial-dependent and -independent events. CONCLUSION: From the evidence obtained from this study, it is concluded that the BJEE is a promising natural extract to combat colorectal cancer cells (HT29 cells) via induction of apoptosis through activation of extrinsic and intrinsic pathways. Dove Medical Press 2018-03-29 /pmc/articles/PMC5881282/ /pubmed/29636600 http://dx.doi.org/10.2147/DDDT.S155115 Text en © 2018 Bagheri et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Bagheri, Elham
Hajiaghaalipour, Fatemeh
Nyamathulla, Shaik
Salehen, Nur’Ain
The apoptotic effects of Brucea javanica fruit extract against HT29 cells associated with p53 upregulation and inhibition of NF-κB translocation
title The apoptotic effects of Brucea javanica fruit extract against HT29 cells associated with p53 upregulation and inhibition of NF-κB translocation
title_full The apoptotic effects of Brucea javanica fruit extract against HT29 cells associated with p53 upregulation and inhibition of NF-κB translocation
title_fullStr The apoptotic effects of Brucea javanica fruit extract against HT29 cells associated with p53 upregulation and inhibition of NF-κB translocation
title_full_unstemmed The apoptotic effects of Brucea javanica fruit extract against HT29 cells associated with p53 upregulation and inhibition of NF-κB translocation
title_short The apoptotic effects of Brucea javanica fruit extract against HT29 cells associated with p53 upregulation and inhibition of NF-κB translocation
title_sort apoptotic effects of brucea javanica fruit extract against ht29 cells associated with p53 upregulation and inhibition of nf-κb translocation
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881282/
https://www.ncbi.nlm.nih.gov/pubmed/29636600
http://dx.doi.org/10.2147/DDDT.S155115
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