Characterization of a human myeloid leukemia cell line highly resistant to taxol

Kapil Bhalla, Vue Huang, Caroline Tang, Sally Self, Swapan Ray, Mary Ella Mahoney, Vidyashankar Ponnathpur, Elena Tourkina, Ana Maria Ibrado, Gloria Bullock, Mark C. Willingham

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Taxol-resistant sublines of HL-60 myeloid leukemia cells (HL-60/TAX100 and HL-60/TAX1000) have been isolated in vitro by subculturing in progressively higher concentrations of taxol. HL-60/TAX100 and HL-60/TAX1000 cells are capable of continuous growth in the presence of 0.1 μM and 1.0 μM taxol, respectively, and the IC50 (50% growth inhibitory dose) values for taxol for the two sublines are 0.34 and 2.44 μM as compared to 3.1 nM for the parent HL-60 cells. HL-60/TAX100 and HL-60/TAX1000 cells display a variable degree of cross-resistance to taxotere, vincristine and doxorubicin, but are sensitive to the antimetabolite Ara-C. Both HL-60/TAX100 and HL-60/TAX1000 cells over-express MDR-1 m-RNA and the membrane efflux multidrug transporter P-glycoprotein (PGP), as determined by Western blot and immunofluorescence labeling with anti-PGP antibodies. Consequently, exposure of the taxol-resistant cells to [3H]taxol or daunomycin results in the accumulation of significantly lower levels of the two drugs. Co-treatment with cyclosporine (0.5 μg/ml) or verapamil (10 μM) partially overcomes taxol resistance in HL-60/TAX1000 cells. Following treatment with clinically relevant concentration of taxol (1.0 μM for 24 h), HL-60 but not HL-60/TAX1000 cells display intracellular microtubular bundling, markedly enhanced accumulation of the cells in G2/M phase of cell-cycle and internucleosomal DNA fragmentation associated with apoptosis which is independent of bcl-2 gene expression. These taxol-resistant myeloid leukemia cells may serve as in vitro experimental models for examining strategies which may have potential applicability for overcoming taxol resistance.

Original languageEnglish (US)
Pages (from-to)465-475
Number of pages11
JournalLeukemia
Volume8
Issue number3
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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