Ethyl 2-anilino-4-oxo-4,5-dihydrofuran-3-carboxylate exhibits anti-proliferative activity and induces apoptosis in promyelocytic leukemia HL-60 cells.

Furoquinolone and its derivatives exhibit antimicrobial, anti-allergic, anti-inflammatory and anticancer properties. The present study investigated the anti-tumor activity of synthesized intermediates of furoquinolone in human promyelocytic leukemia HL-60 cells. The biological effects of the active compound ethyl 2-anilino-4-oxo-4,5-dihydrofuran-3-carboxylate (compound 131) were examined in HL-60 cells. The following properties were analyzed: Cell survival, cell cycle profile, caspase-3 activity, Bax and Bcl-2 expression, the amount of intracellular Ca2+, the number of reactive oxygen species (ROS) and the mitochondrial membrane potential. Compound 131 (50% cytotoxic concentration, 23.5 µM) significantly reduced the proliferation of HL-60 cells and was revealed to induce apoptosis in HL-60 cells in a concentration-dependent manner. Moreover, this was associated with the activation of caspase-3, upregulation of Bax, an increase in intracellular Ca2+ and ROS production, and a decrease in mitochondrial membrane potential and Bcl-2 expression levels. Compound 131, a novel 4,5-dihydrofuran-3-carboxylate, induced apoptosis in HL-60 cells via the increase of intracellular Ca2+ and ROS to alter the mitochondrial membrane potential and the protein level of Bax and Bcl-2, as well as activating caspase-3. The results of the current study indicate that compound 131 may represent a promising compound for the development of anti-leukemia therapeutics.