Myeloma treated by histone deacetylase inhibitor LBH589

08-18-2006

Multiple myeloma could be treated by the histone deacetylase inhibitor LBH589.

"Multiple myeloma represents an incurable disease, for which development of new therapies is required. Here, we report the effect on myeloma cells of LBH589, a new hydroxamic acid-derived histone deacetylase inhibitor," investigators in Spain reported.

"LBH589 was a potent antimyeloma agent (IC50 <40 nmol/L) on both cell lines and fresh cells from multiple myeloma patients, including cells resistant to conventional chemotherapeutic agents," explained P. Maiso and colleagues, University of Salamanca. "In addition, LBH589 potentiated the action of drugs, such as bortezomib, dexamethasone, or melphalan. Using gene array, quantitative PCR, and Western analyses, we observed that LBH589 affected a large number of genes involved in cell cycle and cell death pathways.

"LBH589 blocked cell cycle progression, and this was accompanied by p21, p53, and p57 upregulation. LBH589 induced cell death through an increase in the mitochondrial outer membrane permeability. LBH589 favored apoptosome formation by inducing cytochrome c release, Apaf-1 up-regulation, and caspase-9 cleavage. In addition, LBH589 stimulated a caspase-independent pathway through the release of AIF from the mitochondria. LBH589 down-regulated Bcl-2 and particularly Bcl-X. Moreover, overexpression of Bcl-X in multiple myeloma cells prevented LBH589-induced cell death."

The researchers concluded, "All these data indicate that LBH589 could be a useful drug for the treatment of multiple myeloma patients."

Maiso and colleagues published their study in Cancer Research (The histone deacetylase inhibitor LBH589 is a potent antimyeloma agent that overcomes drug resistance. Cancer Res, 2006;66(11):5781-5789).

For additional information, contact A. Pandiella, University of Salamanca, Center Invest Cancer, National Research Council, Campus Miguel Unamuno, Salamanca 37007, Spain.

The publisher of the journal Cancer Research can be contacted at: American Association Cancer Research, 615 Chestnut St., 17th Floor, Philadelphia, PA 19106-4404, USA.

Keywords: Salamanca, Spain, Histone Deacetylase Inhibitor, LBH589, Drug Development, Drug Resistance, Multiple Myeloma, Oncology, Cancer Therapy.

This article was prepared by Hematology Week editors from staff and other reports. Copyright 2006, Hematology Week via NewsRx.com.