Histone Deacetylase Inhibitor prevents cell growth in Burkitt's lymphoma by regulating PI3K/Akt pathways and leading to up regulation of micro RNA-143, -145 and -101

ABSTRACT: In this study we analyzed gene expression profiles in a well-characterized BL cell line upon treatment with HDACi combined with chemotherapy. The impact on gene expression regulation was broader when HDACi was combined with chemotherapy, than when either therapy was used alone. As expected, treatment interfered in the regulation of cell cycle progression and enhanced cell death. Noteworthy was the effect on members of p53 signaling pathway. The down regulation of PI3KCA and up regulation of p16 were observed at the gene and protein levels, while the inhibition of Akt phosphorylation and the down regulation of c-Myc were confirmed through the analysis of protein levels. As a complementary approach we investigated if HDACi combined with chemotherapy treatment would enhance mir-101, mir-143 and mir-145 levels in BL cell line. This hypothesis was confirmed and we also observed that levels of mir-101, mir-143 and mir-145 were extremely down regulated in BL patients' samples. In this study we demonstrate mechanisms involved in cell cycle arrest upon cell treatment using a combination of HDACi and chemotherapy. We highlight the fact that effective combinations of HDACis with other cytotoxic drugs could improve BL therapy in the future. DNA microarrays were used to access global gene expression modulation upon treatment of Raji BL cell line with VP-16 or NaB and a combination of NaB and VP-16 for 24 hours. Total RNA was extracted using TrizolM-BM-.. Gene expression of treated cells was compared with controls consisting of untreated cells. Microarray analysis was performed using Agilent Whole Human Genome Microarray 4M-CM-^W44K arrays and labeled using the One Color Quick Amp Labeling Kit (Agilent Technologies). Two biological replicates were included for each experimental condition.

ORGANISM(S): Homo sapiens

SUBMITTER: Patricia Severino 

PROVIDER: E-GEOD-48399 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress