2-acetylfuranonaphthoquinone and Leukemia--Myeloid--Acute

Acute myeloid leukemia (AML) is a heterogeneous malignancy of hematopoietic stem cells with poor clinical outcome despite recent improvements in chemotherapy and stem cell transplantation regimens. Thus, new therapeutic agents are urgently needed in order to prolong the disease-free survival of AML patients in clinic. Here, we report that BBI608 is highly active against diverse AML cell lines in vitro and primary samples obtained from patients with AML ex vivo, as well as effective in vivo in AML xenograft models. Meanwhile, the anti-AML property of BBI608 is closely associated with the inhibition of Stat3 pathway and induction of DNA damage. Of note, BBI608 combined with Bcl-2 inhibitor (i.e., ABT-199) exerts a significantly enhanced anti-leukemia effect in BBI608-resistant cell line Kasumi-1. Together, the present findings suggest that BBI608 might represent a potential candidate agent for AML treatment.

Topics: Adolescent; Adult; Aged; Animals; Antineoplastic Agents; Apoptosis; Benzofurans; Cell Line, Tumor; Cell Proliferation; DNA Damage; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Female; G1 Phase Cell Cycle Checkpoints; Humans; Leukemia, Myeloid, Acute; Male; Membrane Potential, Mitochondrial; Mice; Middle Aged; Naphthoquinones; Resting Phase, Cell Cycle; STAT3 Transcription Factor; Time Factors; Xenograft Model Antitumor Assays; Young Adult