The Experts below are selected from a list of 216 Experts worldwide ranked by ideXlab platform
Dulal Panda - One of the best experts on this subject based on the ideXlab platform.
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mechanism of anti cancer activity of Benomyl loaded nanoparticles in multidrug resistant cancer cells
Journal of Biomedical Nanotechnology, 2015Co-Authors: Sudarshan Kini, D Bahadur, Dulal PandaAbstract:Polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles loaded with Benomyl as anticancer drug formulation against multidrug-resistant EMT6/AR1 cells were synthesized by amine-carboxylate reaction. Using transmission electron microscopy, the average size of chitosan-poly(D,L-lactide-co-glycolide) nanoparticles and Benomyl-encapsulated polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles was estimated to be 155 ± 20 nm and 160 ± 25 nm, respectively. Fourier transform infrared spectroscopy revealed that poly(D,L-lactide-co-glycolide) and chitosan are linked by covalent bonds. Zeta potentials of Benomyl-encapsulated polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles at pH 4, 7.2, and 10 were 30 ± 1.8, 19 ± 0.65, and -22 ± 0.15 mV, respectively, indicating the formation of stable, hydrophilic nanoparticles. The release of Benomyl from Benomyl-encapsulated polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles followed pH-dependent kinetics. The uptake of fluorescein isothiocyanate-labeled chitosan-poly(D,L-lactide-co-glycolide) nanoparticles was concentration-dependent in both MCF-7 and multidrug-resistant EMT6/AR1 cells. EMT6/AR1 cells showed 10-fold higher resistance to Benomyl compared to MCF-7 cells; in contrast, Benomyl-encapsulated polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles effectively inhibited proliferation of MCF-7 and EMT6/AR1 cells with a half-maximal inhibitory concentration of 4 ± 0.5 and 9 ± 0.5 pM, respectively. In the presence of a P-glycoprotein inhibitor, the activity of Benomyl was increased, suggesting that Benomyl is a substrate for P-glycoprotein. Further, Benomyl-encapsulated polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles depoly-merized microtubules both in interphase and mitosis. It blocked cell cycle progression at G2/M and induced apoptosis in EMT6/AR1 cells, suggesting that Benomyl-encapsulated polymeric chitosan-poly(D,L-lactide-co-glycolide) nanoparticles have chemotherapeutic activity against multidrug-resistant cancer cells.
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Benomyl and Colchicine Synergistically Inhibit Cell Proliferation and Mitosis: Evidence of Distinct Binding Sites for These Agents in Tubulin †
Biochemistry, 2008Co-Authors: Marie-jeanne Clément, Krishnan Rathinasamy, Elisabeth Adjadj, Flavio Toma, Patrick Curmi, Dulal PandaAbstract:Benomyl, a tubulin-targeted antimitotic antifungal agent, belongs to the benzimidazole group of compounds, which are known to inhibit the binding of colchicine to tubulin. Therefore, Benomyl was thought to bind at or near the colchicine-binding site on tubulin. However, recent mutational studies in yeast and fluorescence studies involving competitive binding of Benomyl and colchicine on goat brain tubulin suggested that Benomyl may bind to tubulin at a site distinct from the colchicine-binding site. We set out to examine whether colchicine and Benomyl bind to tubulin at distinct sites using a human cervical cancer (HeLa) cell line with the thinking that these agents should exert either additive or synergistic activity on cell proliferation if their binding sites on tubulin are different. We found that Benomyl and colchicine synergistically inhibited the proliferation of HeLa cells and blocked their cell cycle progression at mitosis. The synergistic activity of Benomyl and colchicine was also apparent from their strong depolymerizing effects on both the spindle and interphase microtubules when used in combinations, providing further evidence that these agents bind to tubulin at different sites. Using NMR spectroscopy, we finally demonstrated that Benomyl and colchicine bind to tubulin at different sites and that the binding of colchicine seems to positively influence the binding of Benomyl to tubulin and vice versa. Further, an analysis of the saturation transfer difference NMR data yielded an interesting insight into the colchicine−tubulin interaction. The data presented in this study provided a mechanistic understanding of the synergistic effects of Benomyl and colchicine on HeLa cell proliferation.
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Kinetic stabilization of microtubule dynamic instability by Benomyl increases the nuclear transport of p53
Biochemical pharmacology, 2008Co-Authors: Krishnan Rathinasamy, Dulal PandaAbstract:Abstract Using time-lapse confocal microscopy and enhanced green fluorescent protein–tubulin transfected MCF-7 cells, we found that a tubulin-targeted antimitotic agent, Benomyl at its half-maximal proliferation inhibitory concentration (5 μM) strongly suppressed the rate and extent of growing and shortening excursions of individual microtubules in MCF-7 cells without noticeably depolymerizing the microtubule network or decreasing the polymerized mass of tubulin. Further, Benomyl treatment caused an increase in the acetylation level of microtubules suggesting that it stabilizes microtubules. Under the conditions that suppressed the dynamic instability, a sharp increase in the nuclear accumulation of p53 in MCF-7 cells was observed in the presence of Benomyl. Up regulation of bax and the increased nuclear accumulation of p21 upon Benomyl treatment confirmed the activation of p53. Cisplatin caused an increase in the translocation of p53 into the nucleus in the presence of lower effective concentrations of Benomyl while a decrease in the nuclear accumulation of p53 was observed in the presence of high concentrations of Benomyl suggesting that the stabilized microtubules assist in the nuclear transportation of p53. Furthermore, increased localization of the light chain of the minus end directed motor protein dynein was detected on the microtubules in the Benomyl-treated cells indicating that the suppression of microtubule dynamics may influence the binding of dynein on the microtubules and dynein-mediated cargo transport. Together the data indicate that Benomyl inhibits mitosis primarily by suppressing the dynamic instability of microtubules and support the hypothesis that the kinetic stabilization of microtubules enhances the microtubule-mediated transport of p53 into the nucleus.
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suppression of microtubule dynamics by Benomyl decreases tension across kinetochore pairs and induces apoptosis in cancer cells
FEBS Journal, 2006Co-Authors: Krishnan Rathinasamy, Dulal PandaAbstract:We found that Benomyl, a benzimidazole fungicide, strongly suppressed the reassembly of cold-depolymerized spindle microtubules in HeLa cells. Benomyl perturbed microtubule-kinetochore attachment and chromosome alignment at the metaphase plate. Benomyl also significantly decreased the distance between the sister kinetochore pairs in metaphase cells and increased the level of the checkpoint protein BubR1 at the kinetochore region, indicating that Benomyl caused loss of tension across the kinetochores. In addition, Benomyl decreased the intercentrosomal distance in mitotic HeLa cells and blocked the cells at mitosis. Further, we analyzed the effects of Benomyl on the signal transduction pathways in relation to mitotic block, bcl2 phosphorylation and induction of apoptosis. The results suggest that Benomyl causes loss of tension across the kinetochores, blocks the cell cycle progression at mitosis and subsequently, induces apoptosis through the bcl2-bax pathway in a manner qualitatively similar to the powerful microtubule targeted anticancer drugs like the vinca alkaloids and paclitaxel. Considering the very high toxicity of the potent anticancer drugs and the low toxicity of Benomyl in humans, we suggest that Benomyl could be useful as an adjuvant in combination with the powerful anticancer drugs in cancer therapy.
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antimitotic antifungal compound Benomyl inhibits brain microtubule polymerization and dynamics and cancer cell proliferation at mitosis by binding to a novel site in tubulin
Biochemistry, 2004Co-Authors: Kamlesh K Gupta, Jamie Bishop, Austin Peck, Julie C Brown, Leslie Wilson, Dulal PandaAbstract:The antifungal agent Benomyl [methyl-1-(butylcarbamoyl)-2-benzimidazolecarbamate] is used throughout the world against a wide range of agricultural fungal diseases. In this paper, we investigated the interaction of Benomyl with mammalian brain tubulin and microtubules. Using the hydrophobic fluorescent probe 1-anilinonaphthalene-8-sulfonic acid, Benomyl was found to bind to brain tubulin with a dissociation constant of 11.9 +/- 1.2 microM. Further, Benomyl bound to at a novel site, distinct from the well-characterized colchicine and vinblastine binding sites. Benomyl altered the far-UV circular dichroism spectrum of tubulin and reduced the accessibility of its cysteine residues to modification by 5,5'-dithiobis-2-nitrobenzoic acid, indicating that Benomyl binding to tubulin induces a conformational change in the tubulin. Benomyl inhibited the polymerization of brain tubulin into microtubules, with 50% inhibition occurring at a concentration of 70-75 microM. Furthermore, it strongly suppressed the dynamic instability behavior of individual brain microtubules in vitro as determined by video microscopy. It reduced the growing and shortening rates of the microtubules but did not alter the catastrophe or rescue frequencies. The unexpected potency of Benomyl against mammalian microtubule polymerization and dynamics prompted us to investigate the effects of Benomyl on HeLa cell proliferation and mitosis. Benomyl inhibited proliferation of the cells with an IC(50) of 5 microM, and it blocked mitotic spindle function by perturbing microtubule and chromosome organization. The greater than expected actions of Benomyl on mammalian microtubules and mitosis together with its relatively low toxicity suggest that it might be useful as an adjuvant in cancer chemotherapy.
Mikio Chiba - One of the best experts on this subject based on the ideXlab platform.
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Systemic Movement in Herbaceous Plants of Benomyl and Its Methyl Isocyanate Homologue
Journal of Agricultural and Food Chemistry, 1998Co-Authors: Lesley Crawford, Alan W. Bown, Mikio ChibaAbstract:14C-labeled Azindoyle (MBC-MIC), the methyl isocyanate homologue of Benomyl, was found to exhibit more systemic movement than Benomyl in herbaceous plants. Of the total radioactivity applied to the leaf surface, the movement was mainly toward the growing tips, with some sign of downward movement. On broad beans the percentage of translocated activities were 31.5 and 12.0% of that applied for Azindoyle and Benomyl, respectively. Both Azindoyle and Benomyl were relatively stable at the site of application, and after 48 h, the percentages of intact parent compound were 47.5 and 52.2% for Azindoyle and Benomyl, respectively. However, after 48 h, the percentage of parent compound at the translocated site was lower than that at the site of application, at 6.8 and 3.8% for Azindoyle and Benomyl, respectively. Keywords: Azindoyle; Benomyl; Benomyl homologues; systemic movement; radioautographs
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Determination of Benomyl and its degradation products by chromatographic methods in water, wettable powder formulations, and crops
Journal of Chromatography A, 1993Co-Authors: Raj P Singh, Mikio ChibaAbstract:Abstract Chromatographic methods, used for the determination of methyl [1-(butylcarbamoyl)-1H-benzimidazol-2-yl]carbamate (Benomyl) and methyl 1H-benzimidazol-2-ylcarbamate (carbendazim or MBC) in water, wettable powder (WP) formulations, and crops have been discussed. Because of the instability of Benomyl in water and common organic solvents, most methods reported for the analytical determination of Benomyl use an indirect approach. Since the kinetics of degradation of Benomyl in water and common organic solvents is important in the development of analytical methods of Benomyl, kinetic rates of various degradation reactions of Benomyl are also discussed. The methods, based on the conversion of Benomyl into MBC, and stabilization of Benomyl in the presence of excess butyl isocyanate (BIC), will over-estimate Benomyl with wide range of errors. Since MBC is a natural degradation product of Benomyl and is present in different media at varying concentrations with Benomyl, it should be determined individually with the intact concentrations of Benomyl.
Thomas A Zitter - One of the best experts on this subject based on the ideXlab platform.
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resistance to Benomyl and thiophanate methyl in didymella bryoniae from south carolina and new york
Plant Disease, 1998Co-Authors: Anthony P Keinath, Thomas A ZitterAbstract:An initial collection of 7 isolates of Didymella bryoniae were grown on media amended with 0, 1, 3.2, 10, 31.2, or 100 mg Benomyl per liter. Four isolates grew at all five concentrations of Benomyl, but the other 3 isolates did not grow at concentrations > 1 mg/liter. Colony diameter of the four resistant isolates was reduced by 50% at 33.1 mg Benomyl per liter, relative to growth on nonamended medium. Of 394 isolates tested, 182 isolates were resistant to Benomyl; 178 of these resistant isolates were from South Carolina, 1 was from New York, and 3 were from Florida. Of 196 isolates grown on medium amended with 100 mg/liter thiophanate-methyl, 95 were sensitive and 101 were resistant. Essentially all isolates that were resistant to Benomyl were resistant to thiophanate-methyl. In greenhouse tests, watermelon plants were sprayed with 0, 1.5, 15, 150, or 1,500 mg Benomyl per liter and inoculated 1 day later with either a sensitive or a resistant isolate of D. bryoniae. Relative percent leaf area diseased was greater (P≤0.02) for the resistant isolate than for the sensitive isolate at ≥1.5 mg Benomyl per liter. The occurrence of pathogenic, benzimidazole-resistant D. bryoniae in the eastern United States may reduce the effectiveness of benzimidazole fungicides for gummy stem blight management.
Luis Fermín Capitán-vallvey - One of the best experts on this subject based on the ideXlab platform.
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Simultaneous determination of Benomyl and morestan residues in waters by synchronous solid-phase spectrofluorimetry.
Journal of fluorescence, 1995Co-Authors: José Luis Vilchez, Alberto Navalón, Jamal Rohand, Ramiro Avidad, Luis Fermín Capitán-vallveyAbstract:In this paper a new, sensitive, and simple method for simultaneous determination of pesticides morestan and Benomyl at trace levels in waters is reported. Both chemicals, showing native fluorescence in solution at neutral medium, were fixed on C-18 silica gel at pH 1, giving a fluorescent system. The Benomyl-morestan-silica gel system, after dry, was packed in a 1-mm silica cell and its synchronous fluorescence spectra were recorded at δλ=80 nm for determination of Benomyl and δλ=25 nm for determination of morestan. Measurements of fluorescence were performed at λ1=289 nm and λ2=367 nm for Benomyl and morestan analysis, respectively. The applicable concentration ranges were from 0.5 to 15.0 ng·ml−1 for Benomyl and from 0.6 to 15.0 ng·ml−1 for morestan, with relative standard deviations of 1.2 and 1.5% for Benomyl and morestan, respectively, being 0.15 and 0.18 ng·ml−1 its respective detection limits. The method was applied to the simultaneous determination of residues of both pesticides in water of different provenances.
Ahn-heum Eom - One of the best experts on this subject based on the ideXlab platform.
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The Effect of Benomyl Treatments on Ginsenosides and Arbuscular Mycorrhizal Symbiosis in Roots of Panax ginseng
Journal of Ginseng Research, 2009Co-Authors: Ahn-heum EomAbstract:The effects of Benomyl treatment on ginsenoside and arbuscular mycorrhizal (AM) symbiosis in the roots of Panax ginseng that were collected from two sites in Korea were investigated. The ginseng roots that were treated with Benomyl showed different species compositions of AM fungi colonizing the ginseng roots, compared to untreated roots. In the analysis of ginsenoside, Rc was significantly higher in Benomyl untreated roots than in Benomyl treated roots. The results suggest that AM fungal species composition and ginsenosides in ginseng root could be influenced by the Benomyl treatment.