Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.canlet.2010.07.001
Title: Luteolin induces G1 arrest in human nasopharyngeal carcinoma cells via the Akt-GSK-3β-Cyclin D1 pathway
Authors: Ong, C.-S.
Zhou, J. 
Ong, C.-N. 
Shen, H.-M. 
Keywords: Akt
Cell cycle
Cyclin D
Luteolin
Nasopharyngeal carcinoma
Issue Date: 8-Dec-2010
Citation: Ong, C.-S., Zhou, J., Ong, C.-N., Shen, H.-M. (2010-12-08). Luteolin induces G1 arrest in human nasopharyngeal carcinoma cells via the Akt-GSK-3β-Cyclin D1 pathway. Cancer Letters 298 (2) : 167-175. ScholarBank@NUS Repository. https://doi.org/10.1016/j.canlet.2010.07.001
Abstract: Luteolin, a plant flavonoid is known to possess multiple biological activities such as anti-inflammation, anti-allergy, anti-oxidant as well as anti-cancer. At present, the anti-proliferative potential of luteolin has not been fully understood. In this study, we focused on the effect of luteolin on cell cycle regulation in human nasopharyngeal carcinoma (NPC) cells. First, we found that luteolin inhibited cell cycle progression at G1 phase and prevented entry into S phase in a dose- and time-dependent manner. Next, it was found that luteolin treatment led to down-regulation of cyclin D1 via enhanced protein phosphorylation and proteasomal degradation, leading to reduced CDK4/6 activity and suppression of retinoblastoma protein (Rb) phosphorylation, and subsequently inhibition of the transcription factor E2F-1. In search of the molecular mechanisms underlying luteolin-mediated cyclin D1 down-regulation, it was found that luteolin was capable of suppressing Akt phosphorylation and activation, resulting in de-phosphorylation and activation of glycogen synthase kinase-3β (GSK-3β). Activated GSK-3β then targeted cyclin D1, causing phosphorylation of cyclin D1 at Thr286 and subsequent proteasomal degradation. The above findings were reinforced by the fact that luteolin was able to abrogate the effect of insulin on the Akt/GSK-3β/Cyclin D1 pathway, resulting in suppression of insulin-induced cell proliferation. Since Akt is often over-activated in many human cancers including NPC, it is thus believed that data from this study support the potential application of luteolin as a chemotherapeutic or chemopreventive agent in human cancer. © 2010 Elsevier Ireland Ltd.
Source Title: Cancer Letters
URI: http://scholarbank.nus.edu.sg/handle/10635/108455
ISSN: 03043835
DOI: 10.1016/j.canlet.2010.07.001
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

54
checked on Sep 18, 2019

WEB OF SCIENCETM
Citations

50
checked on Sep 18, 2019

Page view(s)

54
checked on Sep 21, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.