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

• Published in: Cancer research (Chicago, Ill.) Vol. 60; no. 13; pp. 3537 - 3541
• Main Authors: IANCU, C, MISTRY, S. J, ARKIN, S, ATWEH, G. F
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.07.2000
• Subjects: Antineoplastic agents; Apoptosis - drug effects; Biological and medical sciences; Cell Division - drug effects; Doxorubicin - toxicity; Fluorouracil - toxicity; General aspects; Humans; K562 Cells; Medical sciences; Microtubule Proteins; Oligodeoxyribonucleotides, Antisense - toxicity; Paclitaxel - toxicity; Pharmacology. Drug treatments; Phosphoproteins - antagonists & inhibitors; Phosphoproteins - genetics; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - metabolism; Spindle Apparatus - drug effects; Stathmin; Tetrahydrofolate Dehydrogenase - genetics; Tetrahydrofolate Dehydrogenase - metabolism; Transfection; Tumor Stem Cell Assay; Antineoplastic agent; Erythroleukemia; Cell proliferation; Drug combination; Taxol; Acute; Cell division; Antisense RNA; Malignant hemopathy; Antisense oligonucleotide; Mitotic spindle; In vitro; Synergism; Myeloproliferative syndrome; Phosphoproteins; Cell cycle; Established cell line; Sensitization; Microtubule; Onc gene; Mechanism of action; Antimitotic; Tumor cell; Apoptosis
• ISSN: 0008-5472; 1538-7445

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.