Effects of plant sterols on human multidrug transporters ABCB1 and ABCC1
Section snippets
Materials and methods
Materials. Dulbecco’s modified Eagle’s medium (D-MEM) and fetal bovine serum (FBS) were purchased from Invitrogen Corp. (Carlsbad, CA). Colchicine, daunorubicin, rhodamine 123, and indomethacin were obtained from Wako Pure Chemical Industries, Ltd (Osaka, Japan). Calcein-AM was provided by Dojindo Laboratories (Kumamoto, Japan). β-Sitosterol, stigmasterol, β-sitostanol, β-cholestanol, N-ethylmaleimide (NEM), and glutathione (GSH) were purchased from Sigma Chemical (St. Louis, MO). MK-571 was
Effects of plant sterols on daunorubicin accumulation in KB-C2 cells
Fig. 1A shows the accumulation of daunorubicin in KB-C2 cells in the presence of 50 μM dietary phytosterols. Guggulsterone increased the cellular accumulation of daunorubicin, which indicates that this phytosterol inhibit the P-gp-mediated efflux of daunorubicin. In contrast, β-sitosterol, campesterol, stigmasterol, β-sitostanol, β-cholestanol, and fucosterol had no effect on the cellular accumulation of daunorubicin. Higher concentrations (100 μM) of β-sitosterol, campesterol, stigmasterol,
Discussion
It is now established that nutrients and phytochemicals can have pronounced impacts on drug absorption, disposition and elimination [15]. Grapefruit juice and the herbal mild antidepressant St. John’s wort (Hypericum perforatum) are a well known example of a food–drug interaction. Some dietary phytochemicals, such as the bioflavonoid quercetin, tea catechins, and ginsenosides, have been evaluated for their potential P-gp inhibitory effects [16], [17]. We have previously reported the inhibitory
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2017, Biochimica et Biophysica Acta - BiomembranesCitation Excerpt :An enhanced transport velocity can also be accompanied by an increase of the ATPase activity, as has been shown for several flavonoids by Leslie et al. and others [47,52,53]. Guggulsterone, a compound derived from the plant Commiphora mukul and analyzed by Nabekura et al., increased MRP1 ATPase activity in high magnitude [54]. The same applies to the endogenous compound GSSG, as this was shown by Mao et al. [55].
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2015, Biomedicine and PharmacotherapyThe modulation of ABC transporter-mediated multidrug resistance in cancer: A review of the past decade
2015, Drug Resistance UpdatesCitation Excerpt :Nobiletin increased the intracellular accumulation of calcein in KB/MRP cells and stimulated the ATPase activity of ABCC1 (Nabekura et al., 2008a). Guggulsterone, resveratrol, sesamin, matairesinol, glycyrrhetinic acid, and ginsenosides are inhibitors of the ABCB1 transporter, but due to the lack of sufficient clinical studies, these compounds are not considered to be candidates for treatment of cancer (Kitagawa et al., 2007; Nabekura et al., 2005, 2008b, 2008c). Sildenafil is a selective PDE-5 inhibitor used to treat erectile dysfunction and pulmonary arterial hypertension (Vardi et al., 2002).
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2014, FitoterapiaCitation Excerpt :Meanwhile, ganoderic acid stimulates the decline in mitochondrial membrane potential and up-regulates p-p53, p53, Bax, caspase-3, and caspase-9, leading to apoptosis in MDR cells [99]. Moreover, P-gp and MRP1-mediated MDR can also be reversed by gypenoside aglycon separated from Gynostemma pentaphyllum [100], Kuguacin J isolated from Momordica charantia [101], and plant sterols [102]. Drug metabolism enzymes are the second line of cellular resistance.