Abstract Title:

Nobiletin down-regulates c-KIT gene expression and exerts anti-leukemic effects on human acute myeloid leukemia cells.

Abstract Source:

J Agric Food Chem. 2018 Dec 3. Epub 2018 Dec 3. PMID: 30507186

Abstract Author(s):

Pei-Yi Chen, Yu-Ting Chen, Wan-Yun Gao, Ming-Jiuan Wu, Jui-Hung Yen

Article Affiliation:

Pei-Yi Chen


Nobiletin, a dietary citrus flavonoid, has been reported to possess several biological activities, such as anti-oxidant, anti-inflammatory and anti-cancer properties. The aim of this study was to investigate the anti-leukemic effects of nobiletin and its underlying mechanisms on human acute myeloid leukemia (AML) cells. We demonstrated that nobiletin (0-100μM) 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±0.11-fold to 0.60±0.15- and 0.34±0.05-fold) by inhibition of KIT promoter activity. The knockdown of c-KIT expression by shRNA attenuated cancer cell growth and induced cell differentiation. Moreover, we found that the overexpression of c-KITabolished nobiletin-mediated cell growth inhibition in leukemia cells. These results indicate that nobiletin exerts anti-leukemic effects through the down-regulation of c-KIT gene expression in AML cells. Finally, we demonstrated that the combination of a conventional AML chemotherapeutic agent, cytarabine, with nobiletin resulted in more reduction of cell viability in AML cells. Our current findings suggest that nobiletin is a novel c-KIT inhibitor and may serve as a chemo-preventive or -therapeutic agent against human AML.

Study Type : In Vitro Study

Print Options

Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2021 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.