Inhibition of the
proteasome has emerged as a clinically effective anticancer therapeutic approach in recent years.
Bortezomib (Velcade®) showed extremely high potency against a wide range of
cancer cell lines.
Ixazomib (MLN9708-MLN2238), the second-generation
proteasome inhibitor, selectivity and potency were similar to that of
bortezomib, is currently being investigated in phase I studies. It shows superior antitumor activity in
hematologic malignancy, especially
multiple myelomas. In this study, for the first time, we evaluated and compared the antiproliferative and apoptotic effects of the novel
proteasome inhibitor MLN2238 (the active form of
MLN9708) with
bortezomib using in vitro
chronic myeloid leukemia. Cytotoxic and apoptotic effects of
MLN2238 and
bortezomib were determined by
trypan blue dye exclusion assays, WST-1 cell proliferation assay, increased AnnexinV-PI binding capacity, changes in
caspase-3 activity and loss of mitochondrial membrane potential (JC-1). Associated with
proteasome pathway NFκB1 and c-myc
mRNA expression levels were examined by the qRT-PCR method. We observed that cytotoxic and apoptotic effects on K562 cells were started at 5 μm of
MLN2238 and 1 μm of
bortezomib after 24 and 48 h. Also,
MLN2238 and
bortezomib downregulated NFκB1 and c-myc
mRNA expression at 24 h. Our result revealed that MLN22238 and
bortezomib had significant cytotoxic and apoptotic effects on K562 cells. Here, we first demonstrate in vitro data that support the development of
MLN2238, by direct comparison with
bortezomib on K562 cells.