In vitro effects of Sutherlandia frutescens water extracts on cell numbers, morphology, cell cycle progression and cell death in a tumorigenic and a non-tumorigenic epithelial breast cell line. J Ethnopharmacol
Department of Physiology, PO Box 2034, University of Pretoria, Pretoria 0001, South Africa. Journal of ethnopharmacology
(Impact Factor: 3).
08/2009; 124(1):45-60. DOI: 10.1016/j.jep.2009.04.013
Sutherlandia frutescens is a South African herb traditionally used for internal cancers, diabetes, a variety of inflammatory conditions and recently to improve the overall health in cancer and HIV/AIDS patients. The in vitro effects of S. frutescens extracts were evaluated on cell numbers, morphology, cell cycle progression and cell death. Dose-dependent studies (2-10 mg/ml) revealed a decrease in malignant cell numbers when compared to their controls. S. frutescens extracts (10 mg/ml) decreased cell growth in a statistically significantly manner to 26% and 49% (P<0.001) in human breast adenocarcinoma (MCF-7) and human non-tumorigenic epithelial mammary gland cells (MCF-12A) respectively after 72 h of exposure. Cell density was significantly compromised and hypercondensed chromatin, cytoplasmic shrinking, membrane blebbing and apoptotic bodies were more pronounced in the MCF-7 cell line. Both S. frutescens-treated cell lines exhibited and increased tendency for acridine orange staining, suggesting increased lysosomal and/or autophagy activity. Flow cytometry showed an increase in the sub G(1) apoptotic fraction and an S phase arrest in both the 5 mg/ml and 10 mg/ml S. frutescens-treated cells. S. frutescens induced an increase in apoptosis in both cell lines as detected by Annexin V and propidium iodide flow cytometric measurement. At 10 mg/ml, late stages of apoptosis were more prominent in MCF-7 S. frutescens-treated cells when compared to the MCF-12A cells. Transmission electron microscopy revealed hallmarks of increased vacuolarization and hypercondensed chromatin, suggesting autophagic and apoptotic processes. The preliminary study demonstrates that S. frutescens water extracts exert a differential action mechanism in non-tumorigenic MCF-12A cells when compared to tumorigenic MCF-7 cells, warranting future studies on this multi-purpose medicinal plant in southern Africa.
Available from: Linda C Prinsloo
- "New chemotherapeutics derived from natural sources or through synthesis must be able to kill cancerous cells with the least amount of damage to neighboring healthy cells and tissues. The assessment of new drug leads in vitro, uses labelbased biochemical assays which assess the viability or death of cells by measuring different enzyme activities, biomarkers and cell morphologies during and after treatments (Le Roux et al., 2011; Stander et al., 2009). "
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ABSTRACT: Fourier Transform Infrared (FTIR) spectroscopy is a label free methodology showing promise in characterizing different types of cell death. Cervical adenocarcinoma (HeLa) and African monkey kidney (Vero) cells were treated with a necrosis inducer (methanol), novel apoptotic inducers (diphenylphosphino gold (I) complexes) and positive control, auranofin. Following treatment, cells stained with annexin-V and propidium iodide were sorted using a Fluorescence Activated Cell Sorter (FACS Aria) to obtain populations consisting of either viable, necrotic or apoptotic cells. Transmission Electron Microscopy confirmed successful sorting of all three populations. Four bands were identified which could discriminate between viable and necrotic cells namely 989cm(-1), 2852cm(-1), 2875cm(-1) and 2923cm(-1). In HeLa cells viable and induced apoptosis could be distinguished by 1294cm(-1), while four bands were different in Vero cells namely; 1626cm(-1), 1741cm(-1), 2852cm(-1) 2923cm(-1). Principal Component Analysis showed separation between the different types of cell death and the loadings plots indicated an increase in an additional band at 1623cm(-1) in dead cells. FTIR spectroscopy can be developed into an invaluable tool for the assessment of specific types of chemically induced cell death with notably different molecular signatures depending on whether the cells are cancerous and mechanism of cell death.
Copyright © 2015. Published by Elsevier Ltd.
Toxicology in Vitro 08/2015; 29(7). DOI:10.1016/j.tiv.2015.08.002 · 2.90 Impact Factor
Available from: Wei Lei
- "Fernandes reported that a hot-water extract of S. frutescens had antioxidant and anti-inflammatory activities both in human neutrophils and in a cell-free system, and these findings were confirmed by other groups (Chen, 2007; Fernandes et al., 2004; Tobwala et al., 2014). A hot-water extract induces apoptosis and autophagic processes in neoplastic cells (e.g., cervical carcinoma and human breast adenocarcinoma MCF-7 cells (Chinkwo, 2005; Stander et al., 2009), which may explain S. frutescens' claimed activity toward certain cancers. "
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ABSTRACT: Sutherlandia frutescens (L.) R. Br. is an indigenous plant of southern Africa that has been traditionally used for various cancers, infections, and inflammatory conditions.
Our aim was to investigate the potential immuno-stimulatory activity of a polysaccharide-enriched fraction (SFPS) from a decoction of S. frutescens.
RAW 264.7 cells (a murine macrophage cell line) were used to determine the activities of SFPS on macrophage function. The production of reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines were evaluated in the cells treated with or without SFPS. CLI-095, a toll-like receptor (TLR) 4-specific inhibitor, was used to identify whether or not SFPS exerts its effects through TLR4. An antagonist of endotoxin, polymyxin B, was used to evaluate whether endotoxin present in SFPS contributed to its immune-stimulatory activity.
SFPS exhibited potent immune-stimulatory activity by macrophages. The production of ROS, NO, and tumor necrosis factor (TNF-α) were increased upon exposure to SFPS in a dose-dependent manner. All of these activities were completely blocked by co-treatment with CLI-095, but only partially diminished by polymyxin B.
We demonstrate for the first time potent immune-stimulatory activity in a decoction prepared from S. frutescens. We believe that this immune stimulatory activity is due, in part, to the action of polysaccharides present in the decoction that acts by way of TLR4 receptors and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. These findings provide a plausible mechanism through which we can understand some of the medicinal properties of S. frutescens.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Journal of ethnopharmacology 06/2015; 172. DOI:10.1016/j.jep.2015.06.013 · 3.00 Impact Factor
Available from: Pius Fasinu
- "It has been investigated for many of the anecdotal claims. Many of such studies have suggested its potential for beneficial effects in HIV/AIDS (Harnett et al., 2005), cancer (Stander et al., 2007, 2009; Skerman et al., 2011), diabetes (Chadwick et al., 2007; Mackenzie et al., 2009, 2012), inflammation (Ojewole, 2004), microbial infection (Katerere and Eloff, 2005), stress (Prevoo et al., 2004), and convulsion (Ojewole, 2008). Commercial twice-daily Sutherlandia capsules containing 300 mg of powdered dried leaves are also available in the herbal medicines shops in South Africa (Van Wyk and Albrecht, 2008). "
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ABSTRACT: Sutherlandia frutescens (ST) is a popular medicinal herb widely consumed in Africa by people living with HIV/AIDS. Concomitant use with antiretroviral drugs has generated concerns of herb-drug interaction. This study investigated the inhibitory effects of the crude extracts of ST on the major cytochrome P450 isozymes employing pooled human liver microsomes. Its effect on the metabolic clearance of midazolam using cryopreserved hepatocytes was also monitored. The potential of ST to inhibit human ATP-binding cassette (ABC) transporters (P-gp and BCRP) and the human organic anion transporting polypeptide (OATP1B1 and OATP1B3) activity was assessed using cell lines overexpressing the transporter proteins. ST showed inhibitory potency for CYP1A2 (IC(50) = 41.0 μg/mL), CYP2A6 (IC(50) = 160 μg/mL), CYP2B6 (IC(50) = 20.0 μg/mL), CYP2C8 (IC(50) = 22.4 μg/mL), CYP2C9 (IC(50) = 23.0 μg/mL), CYP2C19 (IC(50) = 35.9 μg/mL) and CYP3A4/5 (IC(50,) = 17.5 μg/mL [with midazolam1'-hydroxylation]; IC(50) = 28.3 μg/mL [with testosterone 6β-hydroxylation]). Time-dependent (irreversible) inhibition by ST was observed for CYP3A4/5 (KI = 296 μg/mL, kinact = 0.063 min(-1)) under the conditions of this study. ST also delays the production of midazolam metabolites in the hepatocytes, decreasing its clearance by 40%. Further, ST inhibited P-gp (IC(50) = 324.8 μg/mL); OATP1B1 (IC(50) = 10.4 μg/mL, and of OATP1B3 (IC(50) = 6.6 μg/mL). The result indicates the potential for HDI between ST and the substrates of the affected enzymes, if sufficient in vivo concentration of ST is attained.
Drug metabolism and disposition: the biological fate of chemicals 12/2012; 41(2). DOI:10.1124/dmd.112.049593 · 3.25 Impact Factor
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