Nobiletin Down-Regulates c-KIT Gene Expression and Exerts Antileukemic Effects on Human Acute Myeloid Leukemia Cells

Nobiletin, a dietary citrus flavonoid, has been reported to possess several biological activities such as antioxidant, anti-inflammatory, and anticancer properties. The aim of this study was to investigate the antileukemic effects of nobiletin and its underlying mechanisms on human acute myeloid leukemia (AML) cells. We demonstrated that nobiletin (0–100 μM) significantly reduced cell viability from 100.0 ± 9.6% to 31.1 ± 2.8% in human AML THP-1 cell line. Nobiletin arrested cell cycle progression in G1 phase and induced myeloid cell differentiation in human AML cells. Microarray analysis showed that mRNA expression of the c-KIT gene, a critical proto-oncogene associated with leukemia progression, was dramatically reduced in nobiletin-treated AML cells. Furthermore, we verified that AML cells treated with nobiletin (40 and 80 μM) for 48 h markedly suppressed c-KIT mRNA expression (from 1.00 ± 0.07-fold to 0.62 ± 0.08- and 0.30 ± 0.05-fold) and reduced the level of c-KIT protein expression (from 1.00 ± 0.1...