Taxol and anti-stathmin therapy: A synergistic combination that targets the mitotic spindle

Camelia Iancu, Sucharita J. Mistry, Steven Arkin, George F. Atweh

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Stathmin is an abundant cytosolic phosphoprotein that plays an important role in the regulation of cellular proliferation. Its major function is to promote depolymerization of the microtubules that make up the mitotic spindle. Taxol is an effective chemotherapeutic agent whose activity is mediated through stabilization of the microtubules of the mitotic spindle. We demonstrate that antisense inhibition of stathmin expression chemosensitizes K562 leukemic cells to the antitumor effects of Taxol and results in a synergistic inhibition of their growth and clonogenic potential. In the presence of stathmin inhibition, exposure to Taxol results in more severe mitotic abnormalities (hypodiploidy and multinucleation). This, in turn, results in increased apoptosis of the aneuploid cells during subsequent cell division cycles. This novel molecular-based therapeutic approach may provide an effective form of cancer therapy that would avoid the severe toxicities associated with the use of multiple chemotherapeutic agents with overlapping toxicity profiles.

Original languageEnglish
Pages (from-to)3537-3541
Number of pages5
JournalCancer Research
Volume60
Issue number13
StatePublished - 1 Jul 2000

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