A naturally occurring furanocoumarin with diverse biological activities
Bergamottin is a furanocoumarin found in grapefruit juice and lemon, lime, and bergamot oils that has diverse biological activities.1 In vitro, bergamottin inhibits migration and invasion of HT-1080 fibrosarcoma cells at sub-cytotoxic concentrations via inhibition of matrix metalloproteinase-9 (MMP-9) expression.2 It shows antiproliferative activity against HepG2 liver, HL-60 leukemia, and BGC-823 gastric cancer cell lines in a dose-dependent manner and induces cell death of CHO cells following near ultraviolet irradiation.1,3 Bergamottin inhibits the cytochrome P450 isoform 3A4 (CYP3A4; Ki = 7.7 μM) and is a mixed inhibitor of simvastatin drug metabolism (Ki = 174 μM).4,5 It also increases glucose consumption in HepG2 cells in a dose-dependent manner.3
1.Ashwood-Smith, M.J., Ceska, O., Warrington, P.J., et al.The photobiological activity of 5-geranoxypsoralen and its photoproductsPhotochem. Photobiol.55(4)529-532(1992) 2.Hwang, Y.P., Yun, H.J., Choi, J.H., et al.Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by bergamottin via the inhibition of protein kinase Cdelta/p38 mitogen-activated protein kinase and JNK/nuclear factor-kappaB-dependent matrix metalloproteinase-9 expressionMol. Nutr. Food Res.54(7)977-990(2010) 3.Liu, Y., Ren, C., Cao, Y., et al.Characterization and purification of bergamottin from Citrus grandis (L.) Osbeck cv. Yongjiazaoxiangyou and its antiproliferative activity and effect on glucose consumption in HepG2 cellsMolecules22(7)(2017) 4.He, K., Iyer, K.R., Hayes, R.N., et al.Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juiceChem. Res. Toxicol.11(4)252-259(1998) 5.Le Goff-Klein, N., Koffel, J.C., Jung, L., et al.In vitro inhibition of simvastatin metabolism, a HMG-CoA reductase inhibitor in human and rat liver by bergamottin, a component of grapefruit juiceEur. J. Pharm. Sci.18(1)31-35(2003)
Kinase experiment: | CYP1A1 Supersomes and different concentrations of 7-ethoxyresorufin (ER) are used to determine CYP1A1 enzymatic kinetics. A typical Michaelis-Menten curve is found. The final reaction mixture contains: 1 pmol CYP1A1, 0.5 mM NADPH, different ER concentrations and 0, 4, 8 and 16 nM of Bergamottin (BG). The reaction is started with the addition of NADPH. Kinetic constants are obtained by a nonlinear regression analysis of experimental data fitted to Michaelis-Menten equation with competitive-type inhibition. Kinetic analysis is also shown by using the Lineweaver-Burk, Dixon and replot of the slopes of the Dixon plot[1]. |
Cell experiment: | Inhibition of cell proliferation by Bergamottin is measured by the MTT assay. Briefly, the human lung adenocarcinoma cancer A549 cells are plated in 96-well culture plates (1×105 cells/well). After 24 h of incubation, the cells are treated with Bergamottin (0, 5, 10, 25, 50, 75 and 100 μM) for 24 and 48 h, MTT solution (10 mg/mL) is then added to each well. After a 4-h incubation, the formazan precipitate is dissolved in 100 μL DMSO, and then the absorbance is measured in an automated microplated reader at 570 nm. The cell viability ratio is calculated. Cytotoxicity is expressed as the concentration of Bergamottin needed to inhibit cell growth by 50% (IC50 value)[2]. |
Animal experiment: | Mice[2]Female BALB/c nude mice (six weeks old) (a total of 20 are obtained) are maintained with water and food ad libitum in a pathogen-free environment with a 12 h light and 12 h dark cycle in an animal care facility. Human non?small cell lung carcinoma A549 cells (2×106 cells/mouse) are injected into the right axilla of the nude mice (5 mice/group) to create tumors in the mice. Subsequent to tumor development, the mice are divided into 4 groups and treated with Bergamottin injected intraperitoneally. The control group in the study is treated with an equal amount of PBS while the other three groups are treated with 25, 50 and 100 mg/kg of Bergamottin. Afterwards, the mice are sacrificed after 18 days, and the tumor weight and volume of each mouse are evaluated. Tumor length and width are measured using a Vernier caliper and the tumor volume (TV) is calculated[2]. |
参考文献: [1]. Olguín-Reyes S, et al. Bergamottin is a competitive inhibitor of CYP1A1 and is antimutagenic in the Ames test. Food Chem Toxicol. 2012 Sep;50(9):3094-9. | |
动态评分
0.0