Flavonoids kaempferol (KAE) and quercetine (QUE) inhibited proliferation of human leukemia THP-1 cells by up regulation of pro-apoptotic protein Bax and caspase 3/8 expression and down regulation of anti-apoptotic proteins Bcl-2, Bcl-xl and Mcl-1 expression

Abstract

Acute myeloid leukemia (AML) is a type of leukemia robustly affecting the normal proliferation and maturation proce- dure of human hematopoietic myeloid lineage. Nowadays, Flavonoids, well-known types of natural product, because of their acceptable efficacy and lower side effects have attracted increasing consideration in the context of AML therapy using natu- ral products and herbal medicine. Herein, we evaluated flavonoid kaempferol (KAE) and quercetin (QUE) on acute myeloid leukemia THP-1cells proliferation. To address the anti-leukemic potential of KAE and QUE in leukemia THP-1 cells, these cells were treated with KAE (40 µM), QUE (40 µM), and KAE plus QUE within 12, 24, 48, and 72 hours of exposure. Then, cell proliferation was evaluated using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Moreover, expression rates of the pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2, Mcl-1, and Bcl-xL along with caspase 3 and caspase 8 were assessed by real-time PCR (RT-PCR) during 24 and 48 hours of exposure with KAE (40 µM), QUE (40 µM), and KAE plus QUE. After that, the candidate’s gene expression levels were compared with control THP-1 cells. Based on MTT assay results, KAE and QUE at 40 µM concentration reserved proliferation of THP-1 cells compared with control cells, while the anti-proliferative effects of the QUE had superiority over KAE in treated cells. Importantly, results evidenced the synergistic effects of the KAE plus QUE on THP-1 cell proliferation during all periods of the experiment. On the other, these compounds could improve Bax, caspase 3, and caspase 8 expressions, and conversely stimulated a significant and robust reduction in Bcl-2, Mcl-1, and Bcl-xl expression at mRNA levels in the treated cell compared with control cells. In sum, we suggested that the use of the KAE plus QUE could more evidently abrogate proliferation and viability of human leukemia THP-1 cells targeting survival involved genes expression, delivering the proof of the concept that combines the application of KAE and QUE is a rational strategy to treat AML.