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  • Title: The effects of pyrrolo[1,2-b][1,2,5]benzothiadiazepines in MEC1 cells.
    Author: Maffei G, Mirone G, Perna S, Di Stefano C.
    Journal: J Cell Biochem; 2015 Feb; 116(2):339-49. PubMed ID: 25211624.
    Abstract:
    Chronic Lymphocytic Leukemia (CLL) is the most common adult leukemia and is currently incurable. To expand the therapeutic armamentarium, we investigated antitumor activity of pyrrolo[1,2-b][1,2,5]benzothiadiazepine (PBTDs) in MEC1 cells. We found that PBTD (RS2778) treatment enhanced the activation of pro-apoptotic members, such as caspase-9, 3, poly (ADP-ribose) polymerase (PARP), and bax, but suppressed the activation of anti-apoptotic molecule BCL-2 in these cells. Furthermore, PBTD (RS2778)-induced autophagic cell death was verified by LC3-II conversion, and upregulation of Beclin-1 and ATG5. In addition, such compound impeded hyper phosphorylation of AKT as were determined by Western blot. In summary, PBTD (RS2778) inhibited viability and induced multiple cellular events including apoptosis, autophagic cell death, in human MEC1 cells. This distinct activity of PBTD (RS2778) against these cells suggests potential for PBTDs as a therapeutic agent for treatment of CLL.
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