Tubulin-Targeted Drug Action: Functional Significance of Class II and Class IVb β-Tubulin in Vinca Alkaloid Sensitivity

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Tubulin-targeted drug action: functional significance of class ii and class IVb beta-tubulin in vinca alkaloid sensitivity.

Aberrant expression of beta-tubulin isotypes is frequently described in tumor tissues and tubulin-binding agent (TBA)-resistant cell lines. There is limited understanding of the role of specific beta-tubulin isotypes in cellular sensitivity to TBAs, and to gain insights into the functional role of betaII- and betaIVb-tubulin, we examined these isotypes in lung cancer cell lines NCI-H460 (H460) ...

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Tubulin-Targeted Drug Action: Functional Significance of Class II and Class IVb B-Tubulin in Vinca Alkaloid Sensitivity

Aberrant expression of B-tubulin isotypes is frequently described in tumor tissues and tubulin-binding agent (TBA)–resistant cell lines. There is limited understanding of the role of specific B-tubulin isotypes in cellular sensitivity to TBAs, and to gain insights into the functional role of BIIand BIVb-tubulin, we examined these isotypes in lung cancer cell lines NCI-H460 (H460) and Calu-6. Dr...

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Inhibition of tubulin-microtubule polymerization by drugs of the Vinca alkaloid class.

A series of Vinca alkaloids were found to block polymerization of crude tubulin extracts of porcine brain in a dose-dependent manner. This appears to be a specific effect occurring at low concentrations of drug. The concentration of vinblastine that prevents polymerization by 50% was 4.3 x 10(-7) mole/liter for a tubulin concentration of 3.0 mg/ml, and this concentration is consistent with leve...

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Energetics of vinca alkaloid interactions with tubulin isotypes: implications for drug efficacy and toxicity.

A number of vinca alkaloids, including vincristine, vinblastine, and vinorelbine, are currently used in cancer chemotherapy. These three vinca alkaloids interact differently with a range of solid and hematologic tumors. To test the possibility that the tubulin isotype composition is an important determinant in antineoplastic efficacy, we determined thermodynamic parameters for vinca alkaloid in...

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Overexpression of class I, II or IVb beta-tubulin isotypes in CHO cells is insufficient to confer resistance to paclitaxel.

Recent studies have suggested a correlation between increased expression of specific beta-tubulin isotypes and paclitaxel resistance in drug-selected cell lines. In an attempt to establish a causal link, we have transfected Chinese hamster ovary cells with cDNAs encoding epitope-tagged class I, II, and IVb beta-tubulins, as well as a class I beta-tubulin with a mutation previously characterized...

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ژورنال

عنوان ژورنال: Cancer Research

سال: 2008

ISSN: 0008-5472,1538-7445

DOI: 10.1158/0008-5472.can-08-1501