Tubulin alterations in taxol-induced apoptosis parallel those observed with other drugs
Abstract
We have described previously that during apoptosis cellular tubulin is reorganized into visible tubulin structures that correlate with apoptotic morphology. Such changes have been observed in human leukaemic cells treated with a variety of cytotoxic agents. These structures are unlike those seen in untreated non-mitotic or mitotic cells. As taxol is known to act by enhancing the polymerization of tubulin in the initiation and extension of microtubules (MTs), and has been shown to induce and stabilize the formation of tubulin structures in a variety of cells, we examined the involvement of tubulin in apoptosis induced by taxol. Apoptosis was induced in a human T-cell leukaemic line, CCRF-CEM, following treatment with 10 nM taxol. The morphological features typical of apoptosis were apparent in taxol-treated cells after drug addition. Immunocytochemical analysis using a monoclonal antibody to beta-tubulin indicated that taxol induced visible tubulin polymerization. DNA fragmentation was detected at 10 hr post-treatment. Flow cytometric analysis of taxol-treated cells showed a time-dependent accumulation of cells in G2/M phase with the appearance of a hypodiploid peak coincident with the detection of DNA fragmentation. Microtubule...Continue Reading
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis