Histone deacetylase inhibitors (HDAC-I) are a group of small molecules that have been intensively investigated in a variety of malignancies because of their ability to induce a broad range of effects preferentially on cancer cells, including cell cycle arrest, apoptosis, cell differentiation, autophagy and anti-angiogenic effects. However, clinical responses have been obtained only in a proportion of patients, prompting further studies aimed at identifying more active compounds. Here we investigated the effects of two new HDAC-I, MS-275 and ST7612AA1 (doses ranging from 5 to 5000nM) on cell proliferation and apoptosis in acute leukemia cell line models (U937, MOLT4, Jurkat, Raji) and on freshly isolated AML samples. The cytotoxic effects were assessed by MTT assay. The drug concentration inducing 50% cell killing (IC-50) was calculated from the dose-response curve. Cell cycle inhibition and induction of apoptosis were analyzed by flow cytometry using the Acridine-Orange (AO) and Annex
Novel Histone Deacetylase (HDAC) inhibitors: in vitro effects on leukemic cells / Licchetta, Roberto; Ricciardi, Maria Rosaria; Mirabilii, Simone; Allegretti, Matteo; M., Vincenzi; G., Giannini; C., Pisano; L., Vesci; Tafuri, Agostino. - In: HAEMATOLOGICA. - ISSN 0390-6078. - ELETTRONICO. - (2013). (Intervento presentato al convegno 44° Congresso Nazionale SIE tenutosi a Verona nel 20-23 Ottobre 2013).
Novel Histone Deacetylase (HDAC) inhibitors: in vitro effects on leukemic cells
LICCHETTA, ROBERTO;RICCIARDI, Maria Rosaria;MIRABILII, SIMONE;ALLEGRETTI, MATTEO;TAFURI, Agostino
2013
Abstract
Histone deacetylase inhibitors (HDAC-I) are a group of small molecules that have been intensively investigated in a variety of malignancies because of their ability to induce a broad range of effects preferentially on cancer cells, including cell cycle arrest, apoptosis, cell differentiation, autophagy and anti-angiogenic effects. However, clinical responses have been obtained only in a proportion of patients, prompting further studies aimed at identifying more active compounds. Here we investigated the effects of two new HDAC-I, MS-275 and ST7612AA1 (doses ranging from 5 to 5000nM) on cell proliferation and apoptosis in acute leukemia cell line models (U937, MOLT4, Jurkat, Raji) and on freshly isolated AML samples. The cytotoxic effects were assessed by MTT assay. The drug concentration inducing 50% cell killing (IC-50) was calculated from the dose-response curve. Cell cycle inhibition and induction of apoptosis were analyzed by flow cytometry using the Acridine-Orange (AO) and AnnexI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
