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Open AccessArticle

St. John’s Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway

1
Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
2
Hisol Inc., 247-9, Baraebong-gil, Unbong-eup, Namwon-si, Jeollabuk-do 55717, Korea
3
Department of Food and Nutrition, Mokpo National University, 1666, Yeongsan-ro, Cheonggye-myeon, Muan-gun, Jeollanam-do 58554, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(4), 966; https://doi.org/10.3390/ijms19040966
Received: 13 February 2018 / Revised: 19 March 2018 / Accepted: 21 March 2018 / Published: 23 March 2018
(This article belongs to the Special Issue Natural Bioactives and Phytochemicals in Cancer Prevention)
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. View Full-Text
Keywords: St. John’s Wort; breast cancer; growth inhibition; AMPK/mTOR; mitochondrial pathway St. John’s Wort; breast cancer; growth inhibition; AMPK/mTOR; mitochondrial pathway
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MDPI and ACS Style

You, M.-K.; Kim, H.-J.; Kook, J.H.; Kim, H.-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. Int. J. Mol. Sci. 2018, 19, 966.

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