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St. John’s Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway
St. John’s Wort (SJW) has been used as an estrogen agonist in the systems affected by menopause. Also, hypericin, a bioactive compound of SJW, has been used as a photosensitizer in photodynamic therapy. In the present study, we investigate the anti-proliferative and pro-apoptotic effects of SJW to d...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979501/ https://www.ncbi.nlm.nih.gov/pubmed/29570671 http://dx.doi.org/10.3390/ijms19040966 |
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author | You, Mi-Kyoung Kim, Hwa-Jin Kook, Ji Hyun Kim, Hyeon-A |
author_facet | You, Mi-Kyoung Kim, Hwa-Jin Kook, Ji Hyun Kim, Hyeon-A |
author_sort | You, Mi-Kyoung |
collection | PubMed |
description | St. John’s Wort (SJW) has been used as an estrogen agonist in the systems affected by menopause. Also, hypericin, a bioactive compound of SJW, has been used as a photosensitizer in photodynamic therapy. In the present study, we investigate the anti-proliferative and pro-apoptotic effects of SJW to demonstrate the chemo-preventive effect in human breast cancer cells. MCF-7 cells were cultured with DMSO or various concentrations of SJW ethanol extract (SJWE). Cell viability, proliferation, apoptosis, the expression of proteins involved in cell growth and apoptosis, and caspase-3/7 activity were examined. SJWE dose-dependently suppressed cell growth and induced apoptosis of MCF-7 cells. Mechanistically, SJWE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and decreased the expression of p-mammalian target of rapamycin (p-mTOR) and p-eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). Also, SJWE inhibited the phosphorylation of protein kinase B (Akt) and showed increases in the expression of pro-apoptotic proteins Bax and Bad with decreases in the expression of anti-apoptotic proteins including B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), and p-Bcl-2-associated death promoter (p-Bad). SJWE at 50 μg/mL showed markedly enhanced caspase-7 activation. Taken together, our results provide evidence that SJWE shows anti-proliferative and pro-apoptotic effects via inhibition of AMPK/mTOR and activation of a mitochondrial pathway. Therefore, SJWE can be used as a chemo-preventive agent without photo-activation. |
format | Online Article Text |
id | pubmed-5979501 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-59795012018-06-10 St. John’s Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway You, Mi-Kyoung Kim, Hwa-Jin Kook, Ji Hyun Kim, Hyeon-A Int J Mol Sci Article St. John’s Wort (SJW) has been used as an estrogen agonist in the systems affected by menopause. Also, hypericin, a bioactive compound of SJW, has been used as a photosensitizer in photodynamic therapy. In the present study, we investigate the anti-proliferative and pro-apoptotic effects of SJW to demonstrate the chemo-preventive effect in human breast cancer cells. MCF-7 cells were cultured with DMSO or various concentrations of SJW ethanol extract (SJWE). Cell viability, proliferation, apoptosis, the expression of proteins involved in cell growth and apoptosis, and caspase-3/7 activity were examined. SJWE dose-dependently suppressed cell growth and induced apoptosis of MCF-7 cells. Mechanistically, SJWE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and decreased the expression of p-mammalian target of rapamycin (p-mTOR) and p-eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). Also, SJWE inhibited the phosphorylation of protein kinase B (Akt) and showed increases in the expression of pro-apoptotic proteins Bax and Bad with decreases in the expression of anti-apoptotic proteins including B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), and p-Bcl-2-associated death promoter (p-Bad). SJWE at 50 μg/mL showed markedly enhanced caspase-7 activation. Taken together, our results provide evidence that SJWE shows anti-proliferative and pro-apoptotic effects via inhibition of AMPK/mTOR and activation of a mitochondrial pathway. Therefore, SJWE can be used as a chemo-preventive agent without photo-activation. MDPI 2018-03-23 /pmc/articles/PMC5979501/ /pubmed/29570671 http://dx.doi.org/10.3390/ijms19040966 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article You, Mi-Kyoung Kim, Hwa-Jin Kook, Ji Hyun Kim, Hyeon-A St. John’s Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway |
title | St. John’s Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway |
title_full | St. John’s Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway |
title_fullStr | St. John’s Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway |
title_full_unstemmed | St. John’s Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway |
title_short | St. John’s Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway |
title_sort | st. john’s wort regulates proliferation and apoptosis in mcf-7 human breast cancer cells by inhibiting ampk/mtor and activating the mitochondrial pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979501/ https://www.ncbi.nlm.nih.gov/pubmed/29570671 http://dx.doi.org/10.3390/ijms19040966 |
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