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

Abstract

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 revealed 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.

The comparison analysis of polyphyllin I and its analogues induced apoptosis of colon and lung cancer cells via mitochondrial dysfunction

“…Icariin, a flavonoid isolated from Epimedium , was reported to inhibit the ovarian cancer cell proliferation, invasion and migration, likewise induce the cell apoptosis through AKT/Mtor/ATG5 signalling pathway 2 . Aescin, a coumarin glycoside compound isolated from the bark of the cane EAG, exhibited the anti‐proliferative activity towards Jurkat leukaemia cells through cell cycle arrest 3 . These studies indicated that the bioactive ingredients extracted from the TCM were promising resources, which could be utilized as nutraceuticals.…”

Antitumor Effects of Esculetin, a Natural Coumarin Derivative, against Canine Mammary Gland Tumor Cells by Inducing Cell Cycle Arrest and Apoptosis

“…Esculetin, a coumarin derivative, reportedly has several biological and pharmacological activities, including antioxidant, anti-inflammatory, and antiedema effects [ 22 , 29 ]. Moreover, recent studies have reported the anticancer effects of esculetin against various human cancers, including lung cancer [ 30 , 31 ], colorectal cancer [ 27 , 32 , 33 ], gastric cancer [ 34 ], and leukemia [ 35 , 36 , 37 , 38 ]. In particular, it is noteworthy in the antitumor effect of esculetin in human breast cancer, the counterpart of canine mammary cancer.…”