Synergistic interaction of lovastatin and paclitaxel in human cancer cells

Sarah A. Holstein, Raymond J. Hohl

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

The hydroxymethylglutaryl-CoA reductase inhibitor lovastatin is used widely to treat hypercholesterolemia and has been shown to have cell cycle-specific effects. In these studies, we have examined the effects of combining lovastatin and paclitaxel (Taxol), a microtubule-stabilizing agent, in the human leukemia K562 and HL-60 cell lines. Isobologram analysis of cytotoxicity assays revealed that there is a synergistic interaction between the two agents in both cell lines. Cell cycle analyses showed that lovastatin enhances paclitaxel-induced G2-M arrest in both cell lines. In addition, Annexin V apoptotic studies revealed that lovastatin enhances paclitaxel-induced apoptosis in HL-60 cells. Lovastatin did not affect levels of [3H]paclitaxel in cells. Whereas lovastatin induced an accumulation of unmodified Ras and caused an upregulation of both RhoB and Rap1A, paclitaxel was found to have no effect on the isoprenylated proteins. Studies of the centromere-associated protein mitosin revealed that treatment with lovastatin and paclitaxel resulted in increased mitosin levels and that lovastatin altered the association of mitosin with condensed chromosomes. These findings provide insight into the mechanisms underlying the cell cycle effects of lovastatin and support the development of a novel therapeutic strategy directed toward altering deleterious cell proliferation.

Original languageEnglish (US)
Pages (from-to)141-149
Number of pages9
JournalMolecular cancer therapeutics
Volume1
Issue number2
StatePublished - Dec 1 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Synergistic interaction of lovastatin and paclitaxel in human cancer cells'. Together they form a unique fingerprint.

  • Cite this