Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily, triggering apoptosis in malignant cell without affecting healthy cells. However, varied types of the cancerous cells (e.g., leukemia) show resistance to TRAIL-induced apoptosis (TIA). Herein, we evaluated the effect of quercetin (QUE) in combination with TRAIL to defeat the resistance of the human acute myeloid leukemia KG-1 cell lines against TIA. Briefly, we treated the KG-1 cells with TRAIL (50 and 250 ng/ml) and QUE (100 μM) alone and in combination together. Then, the expression levels of the pro-apoptotic proteins, including caspase 3, 8, and 9 along with the anti-apoptotic proteins such as survivin and Mcl-1 expressions levels were evaluated by real-time PCR in KG-1 cells 12, 14 and 48 hours upon exposure with TRAIL and QUE (100 μM). Based on results, the combination of TRAIL and QUE augmented the expression levels of the caspase 3, 8, and 9 compared with the cells treated with TRAIL and QUE alone. Conversely, expression rates of the survivin and Mcl-1 were strongly diminished in cells treated with TRAIL plus QUE in comparison to KG-1 cells that treated with TRAIL and QUE alone. Considering finding, QUE can not only improve caspase 3, 8, and 9 when used plus TRAIL, it also made a positive effect on their activation due to the inhibitory impacts on anti-apoptotic protein Mcl-1 and survivin expressions in KG-1 cells, possibly leading to the desired therapeutic outcome in leukemic cells.
