Effects of the microtubule stabilizing agent peloruside A on the proteome of HL-60 cells.

Investigational New Drugs
Anja WilmesJohn H Miller

Abstract

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.

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Citations

Sep 24, 2010·Investigational New Drugs·Anja WilmesJohn Holmes Miller
Oct 13, 2011·Journal of Proteomics·Pei-Hsiu ChenHao-Ai Shui
May 9, 2016·Investigational New Drugs·Ariane ChanJohn H Miller
Apr 13, 2012·PloS One·Puspendu SardarChandan Goswami

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