Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells.

Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells. Abstract Text:

Clara ,Ana M Cosialls,Montserrat ,Daniel Iglesias-Serret,Antonio F , Coll-Mulet, de Frias,Alicia Domingo,Gabriel Pons,Joan Gil,

OBJECTIVE: Antiapoptotic Bcl-2 is overexpressed in most cases of chronic lymphocytic leukemia (CLL). The inhibition of the antiapoptotic Bcl-2 proteins is an attractive strategy for either restoring normal apoptotic process in cancer cells or making these cells more susceptible to conventional chemotherapy. We studied the effect of Bcl-2 inhibitors on the viability of cells from CLL and other mature B-cell neoplasms. MATERIALS AND METHODS: We studied the cytotoxic effects of four nonpeptidic cell-permeable Bcl-2 inhibitors (HA14-1, antimycin A, GX15-003, and GX15-070) on B cells from patients with CLL, mantle cell lymphoma (MCL), and splenic marginal zone lymphoma (SMZL). Moreover, we analyzed the effect of these inhibitors in combination with fludarabine or chlorambucil. RESULTS: HA14-1 induced apoptosis with an EC50 lower than 50 microM in 26 of the 36 CLL samples analyzed. The mean EC50 for these sensitive patients was 23 +/- 2 microM. Antimycin A induced apoptosis in 13 of the 18 CLL samples analyzed. Both HA14-1 and antimycin A induced cytochrome c release from mitochondria and caspase-3 activation. Moreover, HA14-1 induced apoptosis in peripheral cells from MCL and SMZL. HA14-1 also induced apoptosis in CLL samples with alterations in p53 or ATM. Finally, GX compounds induced apoptosis in B cells from 9 of the 11 CLL samples tested. The combination of either HA14-1, antimycin A, or GX compounds with fludarabine or chlorambucil had additive cytotoxic effects on CLL cells. CONCLUSION: Bcl-2 inhibitors induce apoptosis in CLL cells ex vivo and could be used in CLL as monotherapy or given in combination with current chemotherapy.

Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells. Publishing Authors By Initials

C ,AM Cosialls,M ,D Iglesias-Serret,AF ,L Coll-Mulet,M de Frias,A Domingo,G Pons,J Gil,

For similar neoplasms: neoplasms by site: splenic neoplasms research abstracts see: neoplasms: neoplasms by site: splenic neoplasms research

PUBMED ID PMID:

MEDLINE DATE:

Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Experimental hematology

VOLUME: 34

Page Numbers: 1663-9

Journal Abbreviation: Exp. Hematol.

ISSN: 0301-472X

DAY: 27

MONTH: Dec

YEAR: 2006

Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 402313

Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells. Keywords Mesh Terms:

KEYWORDS: Splenic Neoplasms

MESH TERMS: metabolism

Chemical & Substance for Abstract: Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells. Information

Substance Name: Antimycin A

Registry Number: 642-15-9

Grant and Affiliation Information for Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells.

AFFILIATION: Departament de Ciències Fisiològiques II, IDIBELL-Universitat de Barcelona, L'Hospitalet de Llobregat, Spain.

Country: Netherlands

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Exp Hematol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells Related Publications

• Activation of bile acid biosynthesis by the p38 mitogen-activated protein kinase (MAPK): hepatocyte nuclear factor-4alpha phosphorylation by the p38 MAPK is required for cholesterol 7alpha-hydroxylase expression.
• Alterations in plasma and tissue lipids associated with obesity and metabolic syndrome.
• Analysis of the Essential Oil from Helichrysum picardii.
• Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells.
• Development of a biodegradable bioadhesive containing urethane groups.
• Development of insulin resistance and its relation to diet in the obese child.
• Differences in fine-scale genetic structure and dispersal in Quercus ilex L. and Q. suber L.: consequences for regeneration of mediterranean open woods.
• Differential protein expression of murine macrophages upon interaction with Candida albicans.
• Effect of memantine on neuroretinal function and retinal vascular changes of streptozotocin-induced diabetic rats.
• Effectiveness and Safety of Amlodipine in Newly Diagnosed Hypertensive Patients and in Previously Diagnosed Hypertensive Patients not Controlled with their Usual Treatment (NOTA Study).
• Experimental problems in Raman spectroscopy applied to pigment identification in mixtures.
• Extracellular fluid expansion during parenteral refeeding.
• Immobilization of drugs for glaucoma treatment.
• In vitro response to Candida albicans in cultures of whole human blood from young and aged donors.
• Influence of the chemical structure on mobility of PCB congeners in female and male sardine (Sardina pilchardus) from Portuguese coast.
• Oxidized nickel-titanium foams for bone reconstructions: chemical and mechanical characterization.
• Potential microbial risk factors related to soil amendments and irrigation water of potato crops.
• Potential of NMR spectroscopy for the study of human amniotic fluid.
• Proteomic analysis of detergent-resistant membranes from Candida albicans.
• Quantitation of free and glycosidically bound volatiles in and effect of glycosidase addition on three tomato varieties (Solanum lycopersicum L.).
• Reconstructing signal transduction pathways: challenges and opportunities.
• Report. Proteomics Education, an Important Challenge for the Scientific Community: Report on the Activities of the EuPA Education Committee.
• Ten-year trends in self-rated health among spanish adults with diabetes, 1993 2003.
• The Vietnamese Khin population harbors particular N-acetyltransferase 2 allele frequencies.
• The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells.
• The presence of a caregiving relative implicated in the administration of antiretroviral drug administration improves virologic response.
• [Cytoimmunological changes in the bronchoalveolar lavage in asbestos exposure patients]
• [Self-consciousness, consciousness of the other and dementias]
• [Trends in effects of maximum temperatures on organic-cause mortality in Castile-La Mancha, Spain from 1975 to 2003]
• [Utility of amylase serum and urine activity in acute biliary pancreatitis treated with biliary sphincterotomy]