earticle

영어

Recently, it was demonstrated that glycosylation of phenolic compounds enhances their aqueous solubility while retaining biological activities. We synthesized a glycosylated derivatives (AEG) of aloe emodin (AE), which is one of phenolic compounds present in aloe plant, by enzymatic modification and studied its in vitro and in vivo anti-cancer effects against human lung cancer using A549 cells. While treatment of cells with 5 μM AE did not affect the viability of A549 cells, AEG reduced cell viability, with a 40% reduction at the same concentration. Western blot analysis showed that AEG significantly induces the activation of caspase 9 and poly (ADP-ribose) polymerase (PARP) by 3.4 and 2.1-folds, respectively, compared to those in AE-treated cells, suggesting that the cytotoxicity of AEG is associated with apoptotic events. The molecular mechanisms involved in the anti-cancer effect of AEG were investigated by western blot analysis. AEG (5 μM) decreased phosphorylation of ERK, p38 and Akt, by 35, 44, and 57%, respectively, compared to untreated control cells. In addition, whether AEG is equally active against A549 lung cancer cell xenograft tumors was examined in a mouse model. Administration of AEG through intraperitoneal injection to BALB/c-nu mice bearing A549 cells dose-dependently reduced tumor growth. The histological analysis of tumor tissues with H&E staining showed that AEG decreased the cell numbers in tumor tissues and TUNEL assay showed DNA fragmentation of tumor cells. Taken collectively, these results clearly demonstrated that glycosylated aloe emodin inhibits the tumor growth by induction of apoptotic cell death in vitro and in vivo, suggesting that it can be a good candidate as a potent anti-cancer agent against human lung cancer.