Disruption of autophagy by the histone deacetylase inhibitor MGCD0103 and its therapeutic implication in B-cell chronic lymphocytic leukemia.

ABSTRACT: Evading apoptosis is a hallmark of B-cell chronic lymphocytic leukemia (CLL) cells and an obstacle to current chemotherapeutic approaches. Inhibiting histone deacetylase (HDAC) has emerged as a promising strategy to induce cell death in malignant cells. We have previously reported that the HDAC inhibitor MGCD0103 induces CLL cell death by activating the intrinsic pathway of apoptosis. Here, we show that MGCD0103 decreases the autophagic flux in primary CLL cells. Activation of the PI3K/AKT/mTOR pathway, together with the activation of caspases, and to a minor extent CAPN1, resulting in cleavage of autophagy components, were involved in MGCD0103-mediated inhibition of autophagy. In addition, MGCD0103 directly modulated the expression of critical autophagy genes at the transcriptional level

SUBMITTER: El-Khoury V 

PROVIDER: S-EPMC4131250 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature