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Abstract
The enzyme 3–hydroxy–3–methylglutaryl coenzyme A (HMG–CoA) reductase, involved in de novo cholesterol synthesis and cell–cycle progression, was identified as a potential mediator of the growth inhibitory effects of retinoic acid on human neuroblastoma. Lovastatin, a nonreversible inhibitor of HMG–CoA reductase, induced extensive cytotoxicity that was restricted to drug–resistant P–glycoprotein–expressing neuroblastoma cell lines. This response was potentiated by dibutyryl cyclic AMP but not retinoic acid. Patients with advanced–stage metastatic neuroblastoma often display an acquired chemoresistant phenotype, which may in part be mediated by P–glycoprotein. Our studies support the application or use of HMG–CoA reductase inhibitors as potential therapeutic agents in the treatment of these patients who are refractory to chemotherapy.Cite this article
Dimitroulakos, J., Yeger, H. HMG–CoA reductase mediates the biological effects of retinoic acid on human neuroblastoma cells: Lovastatin specifically targets P–glycoprotein–expressing cells. Nat Med 2, 326–333 (1996). https://doi.org/10.1038/nm0396-326 