Apoptosis in Leukemic Cells Induced by Anti-proliferative Coumarin Isolated from the Stem Bark of Fraxinus rhynchophylla

Esculetin 6-O-β-D-arabinofuranosyl-(1→6)-β-D-glucopyranoside (EAG) is a coumarin glycoside isolated from the stem bark of Fraxinus rhynchophylla. This study scrutinized the anti-proliferative activity of EAG on blood cancer-derived Jurkat leukemic cells. Cell viability assays in leukemic cancer cells determined that EAG possesses potent anti-proliferative effects. Moreover, treatment with EAG increased the proportion of apoptotic cells, resulted in cell cycle arrest being induced at the subG0/G1 phase, and reduced the proportion of cells present in the S phase. In addition, mitochondrial membrane potential was reduced by EAG in Jurkat cells. Additionally, EAG triggered apoptosis that was mediated by the downregulation of BCL-XL, p-IκBα, and p-p65 expressions in addition to the upregulation of cleaved Caspase 3 and BAX expressions. These findings uncovered that the toxic effect of EAG was mediated by intracellular signal transduction pathways that involved a mechanism in which reactive oxygen species (ROS) were upregulated. Thus, this study concludes that EAG could potentially serve as a therapeutic agent for leukemia.

Keywords: Fraxinus rhynchophylla; ROS; apoptosis; coumarin; cytotoxicity; leukemia.