- Induction of apoptosis and cytotoxicity by raphasatin in human breast adenocarcinoma MCF-7 cells
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Glucoraphasatin (GRH), a glucosinolate present abundantly in the plants of the Brassicaceae family, is hydrolyzed by myrosinase to raphasatin, which is considered responsible for its cancer chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aims of this study are to determine the cytotoxicity of raphasatin, and to evaluate its potential to cause apoptosis and modulate cell cycle arrest in human breast adenocarcinoma MCF-7 cells. The cytotoxicity was determined following incubation of the cells with glucoraphasatin or raphasatin (0-100 μM), for 24,48, and 72 h. GRH displayed no cytotoxicity as exemplified by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. When myrosinase was added to the incubation system to convert GRH to raphasatin, cytotoxicity was evident. Exposure of the cells to raphasatin stimulated apoptosis, as was exemplified by cell shrinkage, membrane blebbing, chromatin condensation, and nuclear fragmentation. Moreover, using Annexin V-FITC assay, raphasatin induced apoptosis, as witnessed by changes in cellular distribution of cells, at different stages of apoptosis; in addition, raphasatin caused the arrest of the MCF-7 cells at the G2 + M phase. In conclusion, raphasatin demonstrated cancer chemopreventive potential against human breast adenocarcinoma (MCF-7) cells, through induction of apoptosis and cell cycle arrest.
- Ibrahim, Muhammad Din,Kntayya, Saie Brindha,Mohd Ain, Nooraini,Iori, Renato,Ioannides, Costas,Razis, Ahmad Faizal Abdull
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- XPO1 protein inhibitors
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The invention discloses an XPO1 (Exportin 1) inhibitor of which the structural formula F is as shown in the specification. The XPO1 inhibitor has very good solubility in water; by taking sulforaphene as a representative, the compounds have extremely high inhibitory activity to XPO1, tiny side effect, and good biosafety and bioavailability, and are very suitable for clinical application, so that the XPO1 inhibitor has a huge potential market space and economic benefits.
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- Cytotoxic and antioxidant activity of 4-methylthio-3-butenyl isothiocyanate from Raphanus sativus L. (Kaiware Daikon) sprouts
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There is high current interest in the chemopreventive potential of Brassica vegetables (cruciferae), particularly due to their content in glucosinolates (GL), which upon myrosinase hydrolysis release the corresponding isythiocyanates (ITC). Some ITCs, such as sulforaphane (SFN) from broccoli (Brassica oleacea italica), have been found to possess anticancer activity through induction of apoptosis in selected cell lines, as well as indirect antioxidant activity through induction of phase II detoxifying enzymes. Japanese daikon (Raphanus sativus L.) is possibly the vegetable with the highest per capita consumption within the Brassicaceae family. Thanks to a recently improved gram scale production process, it was possible to prepare sufficient amounts of the GL glucoraphasatin (GRH) as well as the corresponding ITC 4-methylthio-3-butenyl isothiocyanate (GRH-ITC) from its sprouts. This paper reports a study on the cytotoxic and apoptotic activities of GRH-ITC compared with the oxidized counterpart 4-methylsulfinyl-3-butenyl isothiocyanate (GRE-ITC) on three human colon carcinoma cell lines (LoVo, HCT-116, and HT-29) together with a detailed kinetic investigation of the direct antioxidant/radical scavenging ability of GRH and GRH-ITC. Both GRH-ITC and GRE-ITC reduced cell proliferation in a dose-dependent manner and induced apoptosis in the three cancer cell lines. The compounds significantly (p -1 s-1, respectively (at 298 K in methanol), whereas the corresponding value measured here for the reference antioxidant α-tocopherol was 425 ± 40 M-1 s-1. GRH reacted with H2O2 and tert-butyl hydroperoxide in water (pH 7.4) at 37°C, with rate constants of 1.9 ± 0.3 × 10-2 and 9.5 ± 0.3 × 10-4 M -1 s-1 (paralleling recently developed synthetic antioxidants) being quantitatively (>97%) converted to GRE. It is demonstrated that GRH-ITC has interesting antioxidant/radical scavenging properties, associated with a selective cytotoxic/apoptotic activity toward three human colon carcinoma cell lines, and very limited toxicity on normal human T-lymphocytes.
- Papi, Alessio,Orlandi, Marina,Bartolini, Giovanna,Barillari, Jessica,Iori, Renato,Paolini, Moreno,Ferroni, Fiammetta,Fumo, Maria Grazia,Pedulli, Gian Franco,Valgimigli, Luca
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experimental part
p. 875 - 883
(2009/05/08)
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- Thermal degradation of sulforaphane in aqueous solution
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Sulforaphane, a cancer chemopreventive agent identified from broccoli, was degraded in an aqueous solution at 50 and 100 °C. The reaction mixtures were extracted with methylene chloride and analyzed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). Dimethyl disulfide, S- methyl methylthiosulfinate, S-methyl methylthiosulfonate, methyl (methylthio)methyl disulfide, 1,2,4-trithiolane, 4-isothiocyanato-1- (methylthio)-1-butene, and 3-butenyl isothiocyanate were identified as volatile decomposition products. After methylene chloride extraction, the aqueous layer was dried and silica gel column chromatography was used to separate and purify the nonvolatile decomposition products. The major thermal degradation compound was determined by 1H NMR, 13C NMR, and FAB-MS as N,N'-di(4-methylsulfinyl)butyl thiourea. A possible mechanism for the formation of these products is proposed.
- Jin, Yi,Wang, Mingfu,Rosen, Robert T.,Ho, Chi-Tang
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p. 3121 - 3123
(2007/10/03)
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