title: Paclitaxel effects on the proteome of HL-60 promyelocytic leukemic cells: comparison to peloruside A.
abstract: Paclitaxel (Taxol®), a drug used to treat solid tumors of the breast, ovary and lung, stabilizes microtubules and arrests cells in G(2)/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.
authors.affiliation: Centre for Biodiscovery and School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: Anja
authors.initials: A
authors.lastname: Wilmes
authors.forename: Ariane
authors.initials: A
authors.lastname: Chan
authors.forename: Pisana
authors.initials: P
authors.lastname: Rawson
authors.forename: T
authors.initials: T
authors.lastname: William Jordan
authors.forename: John Holmes
authors.initials: JH
authors.lastname: Miller
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D015536:Down-Regulation; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology*; D040901:Proteomics / Q000379:methods; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007783:Lactones; C489427:MYC protein, human; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; C414085:peloruside A; D017239:Paclitaxel