Hexamethylene bisacetamide inhibits malignant phenotype in T-ALL cell lines.
T acute lymphoblastic leukemia cell lines treated with hexamethylene bisacetamide (HMBA) undergo a delay in cell cycle progression and increase susceptibility to apoptosis, although they never overcome the differentiation block. In accordance with changes in cell cycle and apoptosis, transitory p53 pathway activation commonly occurs. Bcl-2 inhibition further favours the pro-apoptotic effect of HMBA. Notch1 expression is down regulated by reduction of its transcription level. Accordingly, Notch1 protein and transcriptional activity were affected. Even if HMBA generally reduces Notch1 level in T acute lymphoblastic leukemia (T-ALL) cell lines, this does not commonly influence the biological response; in fact all the analysed cell lines, except CEM cells, display no biological effect following DAPT-induced Notch inhibition.
Cecchinato
V
V
Department of Biomedical Science and Technology, University of Milano, via Fratelli Cervi 93, 20090 Segrate, and Transplant Immunology and Haematology Laboratory, Niguarda-Ca'Granda Hospital, Milano, Italy.
Erba
E
E
Basile
A
A
Scarpati
B
B
Fazi
C
C
Brando
B
B
Comi
P
P
Chiaramonte
R
R
D000081:Acetamides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D051358:Cyclin-Dependent Kinase 4 / Q000032:analysis; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D051881:Receptor, Notch1 / Q000502:physiology; D015398:Signal Transduction; D014280:Triglycerides / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D000081:Acetamides; D000970:Antineoplastic Agents; C497761:NOTCH1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051881:Receptor, Notch1; D014280:Triglycerides; D016159:Tumor Suppressor Protein p53; D005680:gamma-Aminobutyric Acid; C057077:1,2-dilinolenoyl-3-(4-aminobutyryl)propane-1,2,3-triol; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; C014026:hexamethylene bisacetamide