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

Abstract

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.

Red pepper seed water extract inhibits preadipocyte differentiation and induces mature adipocyte apoptosis in 3T3-L1 cells

“…The expression of p-Akt was inhibited by the treatment of LY294002, the inhibitor of PI3K/Akt, for 6 h, and partially recovered at 24 h [ 32 ]. In addition, although, an ethanol extract of St. John's wort reduced p-Akt expression after treatment for 2 h with partial recovery at 6 h, the expression of Bad remained inhibited after 6 h [ 33 ]. In this study, Bad remained inhibited after 24 h of RPS4 exposure ( Fig.…”

St. John’s Wort Suppresses Growth in Triple-Negative Breast Cancer Cell Line MDA-MB-231 by Inducing Prodeath Autophagy and Apoptosis

“…SJWE was prepared using a previously established protocol [ 25 , 26 ] and stored at −20 °C. The triple-negative breast cancer (TNBC) cell line of MDA-MB-231 was purchased from the American Type Culture and Collection (ATCC, Rockville, MD, USA).…”

“…Western blotting was performed as described previously using primary antibodies (LC3, p62, Atg3, Atg5, Atg5-12, Beclin1, PI3Kp85, p-PI3Kp85(Tyr458)/p55(Tyr199), Akt, p-Akt, Bcl-2, Bcl-xL, Bad, p-Bad, Bax, mTOR, p-mTOR, AMPK, p-AMPK, and β-actin) [ 25 ]. Protein expression was detected using a chemiluminescent substrate and quantified with the UVP imaging system (UVP, Upland, CA, USA) using AlphaEaseFC 4.0 (Alpha Innotech, San Leandro, CA, USA).…”

“…A variety of bioactive compounds of SJW ethanol extract (SJWE), including hypericin and hyperforin, have anticancer effects [ 19 , 20 , 21 , 22 , 23 , 24 ]. In addition, we previously reported that SJWE regulated proliferation and apoptosis in MCF-7 breast cancer cells by inhibiting the AMPK/mTOR and Bcl-2 family pathways [ 25 ]. However, the anticancer effect of SJWE in terms of autophagy and apoptosis in TNBC cells is not understood yet.…”

Potentially Beneficial Effects of St. John’s Wort (Hypericum perforatum) in Patients with Metabolic Syndrome

“…The therapeutic effects of SJW and its ingredients have been investigated in many potential indications, including cancer [16][17][18][19][20][21] as well as cardiovascular [22,23], inflammatory, and allergic diseases [24][25][26][27]. However, although the effects of SJW on depression have been extensively studied, its effects on other diseases have not been elucidated.…”