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The Anti-Cancer Activities of Vernonia amygdalina Extract in Human Breast Cancer Cell Lines Are Mediated through Caspase-Dependent and p53-Independent Pathways
Breast cancer is currently the leading cause of cancer-related deaths among women globally. Notably, medicinal plant extracts may be a potential source for treatments of breast cancer. Vernonia amygdalina (VA) is a woody shrub reported to have not only diverse therapeutic effects but also anti-cance...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812032/ https://www.ncbi.nlm.nih.gov/pubmed/24205071 http://dx.doi.org/10.1371/journal.pone.0078021 |
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author | Wong, Fang Cheng Woo, Chern Chiuh Hsu, Annie Tan, Benny Kwong Huat |
author_facet | Wong, Fang Cheng Woo, Chern Chiuh Hsu, Annie Tan, Benny Kwong Huat |
author_sort | Wong, Fang Cheng |
collection | PubMed |
description | Breast cancer is currently the leading cause of cancer-related deaths among women globally. Notably, medicinal plant extracts may be a potential source for treatments of breast cancer. Vernonia amygdalina (VA) is a woody shrub reported to have not only diverse therapeutic effects but also anti-cancer properties. However, current research about the mechanisms of the anti-cancer potential of VA has been limited. This study aimed to investigate the mechanisms of action of VA that underlie its anti-cancer effects in human breast cancer cell lines (MCF-7 and MDA-MB-231 cells). Results from MTT assay revealed that VA inhibits the proliferation of MCF-7 and MDA-MB-231, in a time- and dose-dependent manner. The underlying mechanism of this growth inhibition involved the stimulation of cell-type specific G1/S phase cell cycle arrest in only MCF-7 cells, and not in MDA-MB-231 cells. While the growth arrest was associated with increased levels of p53 and p21, and a concomitant decrease in the levels of cyclin D1 and cyclin E, it was shown that VA causes cell cycle arrest through a p53-independent pathway as tested by the wild type p53 inhibitor, pifithrin-α. Furthermore, this study revealed that VA induces apoptosis in the two cell lines, as indicated by the increase in Annexin V-positive cells and sub-G1 population, and that this VA-induced apoptosis occurred through both extrinsic and intrinsic apoptotic pathways. The apoptosis in MCF-7 cells was also likely to be caspase-dependent and not p53 transcriptional-dependent. Given that approximately 70% of diagnosed breast cancers express ER-α, a crucial finding was that VA inhibits the expression of ER-α and its downstream player, Akt, highlighting the potential clinical significance of VA. Moreover, VA exhibits synergism when combined with doxorubicin, suggesting that it can complement current chemotherapy. Overall, this study demonstrates the potential applications of VA as an anti-cancer drug for breast cancer treatment. |
format | Online Article Text |
id | pubmed-3812032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38120322013-11-07 The Anti-Cancer Activities of Vernonia amygdalina Extract in Human Breast Cancer Cell Lines Are Mediated through Caspase-Dependent and p53-Independent Pathways Wong, Fang Cheng Woo, Chern Chiuh Hsu, Annie Tan, Benny Kwong Huat PLoS One Research Article Breast cancer is currently the leading cause of cancer-related deaths among women globally. Notably, medicinal plant extracts may be a potential source for treatments of breast cancer. Vernonia amygdalina (VA) is a woody shrub reported to have not only diverse therapeutic effects but also anti-cancer properties. However, current research about the mechanisms of the anti-cancer potential of VA has been limited. This study aimed to investigate the mechanisms of action of VA that underlie its anti-cancer effects in human breast cancer cell lines (MCF-7 and MDA-MB-231 cells). Results from MTT assay revealed that VA inhibits the proliferation of MCF-7 and MDA-MB-231, in a time- and dose-dependent manner. The underlying mechanism of this growth inhibition involved the stimulation of cell-type specific G1/S phase cell cycle arrest in only MCF-7 cells, and not in MDA-MB-231 cells. While the growth arrest was associated with increased levels of p53 and p21, and a concomitant decrease in the levels of cyclin D1 and cyclin E, it was shown that VA causes cell cycle arrest through a p53-independent pathway as tested by the wild type p53 inhibitor, pifithrin-α. Furthermore, this study revealed that VA induces apoptosis in the two cell lines, as indicated by the increase in Annexin V-positive cells and sub-G1 population, and that this VA-induced apoptosis occurred through both extrinsic and intrinsic apoptotic pathways. The apoptosis in MCF-7 cells was also likely to be caspase-dependent and not p53 transcriptional-dependent. Given that approximately 70% of diagnosed breast cancers express ER-α, a crucial finding was that VA inhibits the expression of ER-α and its downstream player, Akt, highlighting the potential clinical significance of VA. Moreover, VA exhibits synergism when combined with doxorubicin, suggesting that it can complement current chemotherapy. Overall, this study demonstrates the potential applications of VA as an anti-cancer drug for breast cancer treatment. Public Library of Science 2013-10-24 /pmc/articles/PMC3812032/ /pubmed/24205071 http://dx.doi.org/10.1371/journal.pone.0078021 Text en © 2013 Wong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Wong, Fang Cheng Woo, Chern Chiuh Hsu, Annie Tan, Benny Kwong Huat The Anti-Cancer Activities of Vernonia amygdalina Extract in Human Breast Cancer Cell Lines Are Mediated through Caspase-Dependent and p53-Independent Pathways |
title | The Anti-Cancer Activities of Vernonia amygdalina Extract in Human Breast Cancer Cell Lines Are Mediated through Caspase-Dependent and p53-Independent Pathways |
title_full | The Anti-Cancer Activities of Vernonia amygdalina Extract in Human Breast Cancer Cell Lines Are Mediated through Caspase-Dependent and p53-Independent Pathways |
title_fullStr | The Anti-Cancer Activities of Vernonia amygdalina Extract in Human Breast Cancer Cell Lines Are Mediated through Caspase-Dependent and p53-Independent Pathways |
title_full_unstemmed | The Anti-Cancer Activities of Vernonia amygdalina Extract in Human Breast Cancer Cell Lines Are Mediated through Caspase-Dependent and p53-Independent Pathways |
title_short | The Anti-Cancer Activities of Vernonia amygdalina Extract in Human Breast Cancer Cell Lines Are Mediated through Caspase-Dependent and p53-Independent Pathways |
title_sort | anti-cancer activities of vernonia amygdalina extract in human breast cancer cell lines are mediated through caspase-dependent and p53-independent pathways |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812032/ https://www.ncbi.nlm.nih.gov/pubmed/24205071 http://dx.doi.org/10.1371/journal.pone.0078021 |
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