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Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models
To date, plants have been the major source of anticancer drugs. Boldine is a natural alkaloid commonly found in the leaves and bark of Peumus boldus. In this study, we found that boldine potently inhibited the viability of the human invasive breast cancer cell lines, MDA-MB-231 (48-hour IC(50) 46.5±...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove Medical Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057328/ https://www.ncbi.nlm.nih.gov/pubmed/24944509 http://dx.doi.org/10.2147/DDDT.S58178 |
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author | Paydar, Mohammadjavad Kamalidehghan, Behnam Wong, Yi Li Wong, Won Fen Looi, Chung Yeng Mustafa, Mohd Rais |
author_facet | Paydar, Mohammadjavad Kamalidehghan, Behnam Wong, Yi Li Wong, Won Fen Looi, Chung Yeng Mustafa, Mohd Rais |
author_sort | Paydar, Mohammadjavad |
collection | PubMed |
description | To date, plants have been the major source of anticancer drugs. Boldine is a natural alkaloid commonly found in the leaves and bark of Peumus boldus. In this study, we found that boldine potently inhibited the viability of the human invasive breast cancer cell lines, MDA-MB-231 (48-hour IC(50) 46.5±3.1 μg/mL) and MDA-MB-468 (48-hour IC(50) 50.8±2.7 μg/mL). Boldine had a cytotoxic effect and induced apoptosis in breast cancer cells as indicated by a higher amount of lactate dehydrogenase released, membrane permeability, and DNA fragmentation. In addition, we demonstrated that boldine induced cell cycle arrest at G2/M phase. The anticancer mechanism is associated with disruption of the mitochondrial membrane potential and release of cytochrome c in MDA-MB-231. Boldine selectively induced activation of caspase-9 and caspase-3/7, but not caspase-8. We also found that boldine could inhibit nuclear factor kappa B activation, a key molecule in tumor progression and metastasis. In addition, protein array and Western blotting analysis showed that treatment with boldine resulted in downregulation of Bcl-2 and heat shock protein 70 and upregulation of Bax in the MDA-MB-231 cell line. An acute toxicity study in rats revealed that boldine at a dose of 100 mg/kg body weight was well tolerated. Moreover, intraperitoneal injection of boldine (50 or 100 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that boldine is a potentially useful agent for the treatment of breast cancer. |
format | Online Article Text |
id | pubmed-4057328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40573282014-06-18 Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models Paydar, Mohammadjavad Kamalidehghan, Behnam Wong, Yi Li Wong, Won Fen Looi, Chung Yeng Mustafa, Mohd Rais Drug Des Devel Ther Original Research To date, plants have been the major source of anticancer drugs. Boldine is a natural alkaloid commonly found in the leaves and bark of Peumus boldus. In this study, we found that boldine potently inhibited the viability of the human invasive breast cancer cell lines, MDA-MB-231 (48-hour IC(50) 46.5±3.1 μg/mL) and MDA-MB-468 (48-hour IC(50) 50.8±2.7 μg/mL). Boldine had a cytotoxic effect and induced apoptosis in breast cancer cells as indicated by a higher amount of lactate dehydrogenase released, membrane permeability, and DNA fragmentation. In addition, we demonstrated that boldine induced cell cycle arrest at G2/M phase. The anticancer mechanism is associated with disruption of the mitochondrial membrane potential and release of cytochrome c in MDA-MB-231. Boldine selectively induced activation of caspase-9 and caspase-3/7, but not caspase-8. We also found that boldine could inhibit nuclear factor kappa B activation, a key molecule in tumor progression and metastasis. In addition, protein array and Western blotting analysis showed that treatment with boldine resulted in downregulation of Bcl-2 and heat shock protein 70 and upregulation of Bax in the MDA-MB-231 cell line. An acute toxicity study in rats revealed that boldine at a dose of 100 mg/kg body weight was well tolerated. Moreover, intraperitoneal injection of boldine (50 or 100 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that boldine is a potentially useful agent for the treatment of breast cancer. Dove Medical Press 2014-06-06 /pmc/articles/PMC4057328/ /pubmed/24944509 http://dx.doi.org/10.2147/DDDT.S58178 Text en © 2014 Paydar et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. 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 Paydar, Mohammadjavad Kamalidehghan, Behnam Wong, Yi Li Wong, Won Fen Looi, Chung Yeng Mustafa, Mohd Rais Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models |
title | Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models |
title_full | Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models |
title_fullStr | Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models |
title_full_unstemmed | Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models |
title_short | Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models |
title_sort | evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057328/ https://www.ncbi.nlm.nih.gov/pubmed/24944509 http://dx.doi.org/10.2147/DDDT.S58178 |
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