Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 up-regulation 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.
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PMID:Synergistic interaction of lovastatin and paclitaxel in human cancer cells. 1246 31

Oxysterols have been shown to interfere with proliferation and cause the death of many cancer cell types, such as leukaemia, glioblastoma, colon, breast and prostate cancer cells, while they have little or no effect on senescent cells. The mechanisms by which oxysterols may influence proliferation are manifold: they control the transcription and the turnover of the key enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl CoA reductase, by binding to Insig-1, Insig-2 and liver X receptors. Oxysterols are thought to be generated in proportion to the rate of cholesterol synthesis. Although there is no consensus about the mechanism by which these oxysterols are generated in vivo, it clearly has to be ubiquitous. The 25- and the 27-cholesterol hydroxylases, present in almost all tissues, are possible candidates. Cholesterol uptake from lipoproteins, intracellular vesicle transport and lipid transfer are also modified by oxysterols. Oxysterols interfere with ERK, hedgehog and wnt pathways of proliferation and differentiation. When administered in vitro to cancer cell lines, oxysterols invariably both slow down proliferation and provoke cell death. Perhaps is it sufficient to stop proliferation of a cancer to provoke its eradication. Therefore, the two facets of oxysterol action that seem important for cancer treatment, cytostaticity and cytotoxicity, will be discussed.
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PMID:Oxysterols in cancer cell proliferation and death. 2350 May 45