Investigational New Drugs

, Volume 30, Issue 1, pp 121–129

Paclitaxel effects on the proteome of HL-60 promyelocytic leukemic cells: comparison to peloruside A

  • Anja Wilmes
  • Ariane Chan
  • Pisana Rawson
  • T. William Jordan
  • John Holmes Miller
PRECLINICAL STUDIES

DOI: 10.1007/s10637-010-9540-1

Cite this article as:
Wilmes, A., Chan, A., Rawson, P. et al. Invest New Drugs (2012) 30: 121. doi:10.1007/s10637-010-9540-1

Summary

Paclitaxel (Taxol®), a drug used to treat solid tumors of the breast, ovary and lung, stabilizes microtubules and arrests cells in G2/M of the cell cycle. Using two-dimensional differential in-gel electrophoresis (DIGE), we examined the proteomic response of a human HL-60 promyeloid leukemic cell line to paclitaxel. Our intention was to compare the effects of paclitaxel to those of a new-generation microtubule-stabilizing agent, peloruside A, investigated in an earlier study. In response to 100 nM paclitaxel treatment for 24 h, 21 identified proteins changed in abundance, with 13 increases and 8 decreases. In addition, 21 other unidentified proteins were also changed by treatment with paclitaxel. Using Western blotting, the transcription factor c-Myc was shown to be reduced in abundance by both drugs. Our results showed both differences and similarities at the single protein level between paclitaxel and peloruside A, although the same general classes of proteins: cytoskeletal, nucleic acid binding, stress, and apoptotic proteins, changed following exposure. The proteomic response to paclitaxel was more extensive than the response to an equipotent dose of peloruside A.

Keywords

Cancer Microtubule Paclitaxel Proteome Peloruside c-Myc 

Abbreviations

1DE

One-dimensional electrophoresis

2DE

Two-dimensional electrophoresis

DIGE

Differential in-gel electrophoresis

hnRNP

Heterogeneous nuclear ribonucleoprotein

MALDI-TOF

Matrix-assisted laser desorption ionization time of flight

Pel

Peloruside A

Ptx

Paclitaxel

Supplementary material

10637_2010_9540_MOESM1_ESM.doc (309 kb)
ESM 1(DOC 309 kb)

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Anja Wilmes
    • 1
  • Ariane Chan
    • 1
  • Pisana Rawson
    • 1
  • T. William Jordan
    • 1
  • John Holmes Miller
    • 1
    • 2
  1. 1.Centre for Biodiscovery and School of Biological SciencesVictoria University of WellingtonWellingtonNew Zealand
  2. 2.School of Biological SciencesVictoria University of WellingtonWellingtonNew Zealand

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