Effects of the microtubule stabilizing agent peloruside A on the proteome of HL-60 cells.
Peloruside A, isolated from the marine sponge Mycale hentscheli, has a similar mechanism of action to paclitaxel (Taxol®), a drug used clinically to treat tumors of the breast, ovary and lung. Paclitaxel and peloruside stabilize the polymerized form of tubulin and arrest cells in G₂/M of the cell cycle. We have therefore used two-dimensional electrophoresis of proteins to examine the effect of peloruside A on the human HL-60 promyeloid leukemic cell line. Our goals included investigation whether affected proteins could be mapped onto pathways that predicted the cellular effects of this compound. In response to 100 nM peloruside A treatment for 24 h, seventeen identified proteins showed significant change in abundance with fourteen increases and three decreases. Use of Ingenuity Pathways Analysis confirmed that peloruside A affected pathways consistent with the known effects on microtubules and apoptosis. Our results also indicate a potential role of c-Myc in the cellular actions of peloruside consistent with an induction of aneuploidy seen at low concentrations of peloruside.
Wilmes
Anja
A
Centre for Biodiscovery and School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Rawson
Pisana
P
Peng
Lifeng
L
McLauchlan
Danyl
D
Northcote
Peter T
PT
Jordan
T William
TW
Miller
John H
JH
D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D018922:HL-60 Cells; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism
D019086:Bridged Bicyclo Compounds, Heterocyclic; D007783:Lactones; D009363:Neoplasm Proteins; D020543:Proteome; D016271:Proto-Oncogene Proteins c-myc; D014404:Tubulin; C414085:peloruside A