نتایج جستجو برای: tubulin polymerization
تعداد نتایج: 40472 فیلتر نتایج به سال:
Tubulin and heat shock protein 27 (Hsp27) are well-characterized molecular targets for anti-cancer drug development. We previously identified lead compounds that inhibited both Hsp27 and tubulin. These compounds exhibited extensive anti-cancer activities against the proliferation of various human cancer cell lines. In the current study, a systematic ligand based structural optimization led to n...
Vinca alkaloids, the well-known tubulin-binding agents, are widely used for the clinical treatment of malignant tumors. However, little attention has been paid to their vascular disrupting effects, and the underlying mechanisms remain largely unknown. This study aims to investigate the vascular disrupting effect and the underlying mechanisms of vinca alkaloids. Methods: The capillary disruption...
Microtubules are important components of the cellular cytoskeleton that play roles in various cellular processes such as vesicular transport and spindle formation during mitosis. They are formed by an ordered organization of α-tubulin and β-tubulin hetero-polymers. Altering microtubule polymerization has been known to be the mechanism of action for a number of therapeutically important drugs in...
To understand mechanisms for arsenic toxicity in the lung, we examined effects of sodium m-arsenite (As³⁺) on microtubule (MT) assembly in vitro (0-40 µM), in cultured rat lung fibroblasts (RFL6, 0-20 µM for 24 h) and in the rat animal model (intratracheal instillation of 2.02 mg As/kg body weight, once a week for 5 weeks). As³⁺ induced a dose-dependent disassembly of cellular MTs and enhanceme...
Maximal amounts of tubulin in rat brain are observed during the 3 to 10-day postnatal period. The rates of in vitro tubulin polymerization are very low at these stages of development; they increase thereafter during the second postnatal week, reaching a maximum at adulthood. The increased rate of polymerization could depend either on modifications in the concentration and activity of microtubul...
Bovine brain tubulin was purified by the polymerization method of Shelanski et a!. (19) with some modification as described previously (14). The homogenization buffer was 20 mM 2-(N-morpholino)ethanesulfonate, 70 m@i NaCI, 1 mM EGTA, and 0.5 mM MgCI2, pH 6.4. GTP (0.5 mM) and glycerol (4 M) were added for polymerization. The protein was purified through 2 polymerization cycles and was stored at...
While evaluating a large library of compounds designed to inhibit microtubule polymerization, we identified four compounds that have unique effects on microtubules. These compounds cause mixed effects reminiscent of both microtubule depolymerizers and stabilizers. Immunofluorescence evaluations showed that each compound initially caused microtubule depolymerization and, surprisingly, with highe...
Allicin (diallyl thiosulfinate) is a major biologically active component of garlic that is known to inhibit cell proliferation and induce apoptosis. The effects of allicin are attributed to its ability to react with thiol groups. However, the mechanism underlying the cytostatic activity of allicin, as well as the identity of the relevant subcellular targets, are not known. In the present study,...
Trypanosome tubulin was purified to near homogeneity by chromatography on DEAE-Sephadex, Amicon filtration and assembly-disassembly in vitro. Polymerization of the tubulin in vitro yielded long, structurally normal, microtubules and some sheet structures on addition of GTP and incubation at 37 degrees C, in either the presence or the absence of Mg2+. Tubulin assembly was disrupted by glycerol a...
The isoflavone ME-344 is a potent anti-cancer agent with preclinical and clinical efficacy in solid tumors. Yet, the mechanism of action of ME-344 has not been fully defined and the preclinical efficacy in leukemia has not been established. Therefore, we investigated the anti-leukemic properties and mechanism of action of ME-344. In a panel of 7 leukemia cell lines, ME-344 was cytotoxic with an...
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