Farnesyltransferase Inhibitors: Molecular Evidence of Therapeutic Efficacy in Acute Lymphoblastic Leukemia Through Cyclin D1 Inhibition

Farnesyltransferase inhibitors have the ability to interfere with various intracellular pathways, reducing cell survival and proliferation. They have become an attractive tool for cancer therapy, namely acute leukemias. In this work, we have studied the efficacy of α-hydroxyfarnesylphosphonic acid (...

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Bibliographic Details
Published in:Anticancer research 2012-03, Vol.32 (3), p.831-838
Main Authors: COSTA, Carlos Bruno, CASALTA-LOPES, Joao, SARMENTO-RIBEIRO, Ana B, ANDRADE, Carlos, MOREIRA, Diana, OLIVEIRA, Ana, GONCALVES, Ana C, ALVES, Vera, SILVA, Teresa, DOURADO, Marilia, NASCIMENTO-COSTA, Jose M
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell Line, Tumor
Cyclin D1 - antagonists & inhibitors
Enzyme Inhibitors - pharmacology
Enzyme Inhibitors - therapeutic use
Farnesol - analogs & derivatives
Farnesol - pharmacology
Farnesyltranstransferase - antagonists & inhibitors
Hematologic and hematopoietic diseases
Humans
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Organophosphonates - pharmacology
Phosphorous Acids
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism
Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology
Tumors
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Summary:Farnesyltransferase inhibitors have the ability to interfere with various intracellular pathways, reducing cell survival and proliferation. They have become an attractive tool for cancer therapy, namely acute leukemias. In this work, we have studied the efficacy of α-hydroxyfarnesylphosphonic acid (α-HFPA) in CEM (acute T-cell lymphoblastic leukemia) in culture. CEM cells were incubated with α-HFPA at different concentrations; viability and proliferation studies were performed using the trypan blue exclusion assay and cell morphological analysis. Expression of lamin A/C, cyclin D1 and BAD were analyzed by flow cytometry. Our results show that α-HFPA significantly decreases Farnesyltransferase activity, reduces cell proliferation and induces cell death through apoptosis in CEM cells, which is correlated with a reduction of cyclin D1 levels. This study suggests that α-HFPA blocks the cell cycle and induces cell death through apoptosis in CEM cells and may be a therapeutic approach in ALL.
ISSN:0250-7005
1791-7530