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

Abstract

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.