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Molecular Regulation of Taxane-Induced Apoptosis

Published online by Cambridge University Press:  02 July 2020

K. Bhalla
K. Bhalla*
Affiliation:
Emory University School of Medicine and Winship Cancer Center, Atlanta, GA30322
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Extract

Following intracellular uptake, taxanes bind to β tubulin and suppress microtubular dynamics, resulting in stable microtubule bundles and mitotic arrest of cancer cells. This proximal taxane- β tubulin interaction depends on the amount of intracellular accumulation of taxanes. Since taxanes are substrates for the membrane transporter P-glycoprotein (PGP) but not the MRP, overexpression of PGP but not MRP reduces the intracellular accumulation and cytotoxicity of taxanes. Recent reports have also suggested that alterations in the levels of specific β tubulin isotypes can reduce the effects of taxanes on microtubule dynamics, thereby inhibiting the mitotic effects and resulting cytotoxicity of taxanes.6 For example, increased βIV and (βIII tubulin levels may confer resistance against microtubule and cytostatic effects of taxanes. Taxane-induced G2/M arrest is preceded by the activation of cell-cycle mitotic kinase CDK1, which promotes the G2/M transition. Recent studies have indicated that the loss of cell-cycle Gl checkpoint due to p53 mutations may enhance taxane-induced mitotic arrest and cytotoxicity.

Type
Chemotherapeutic Agents That Affect Microtubules: Mechanisms of Response and Chemotherapeutic Agents and Microtubules
Information
Microscopy and Microanalysis , Volume 4 , Issue S2: Proceedings: Microscopy & Microanalysis '98, Microscopy Society of America 56th Annual Meeting, Microbeam Analysis Society 32nd Annual Meeting, Atlanta, Georgia July 12-16, 1998 , July 1998 , pp. 1040 - 1041
Copyright
Copyright © Microscopy Society of America

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