Abstract Title:

Combination of Nexrutine and Docetaxel suppresses NFκB-mediated activation of c-FLIP.

Abstract Source:

Mol Carcinog. 2017 May 9. Epub 2017 May 9. PMID: 28485511

Abstract Author(s):

Yangang Zhang, Li Li, Jingyu Wang, Wei Cheng, Jiandong Zhang, Xueting Li, Zhenhua Zhang, Jingjing Gong, Rita Ghosh, Addanki Pratap Kumar, Jianping Xie

Article Affiliation:

Yangang Zhang


Lack of effective options following failure to conventional chemotherapeutic agent such as Docetaxel is a major clinical challenge in the management of prostate cancer. These observations underscore the need for deciphering the underlying mechanism of docetaxel resistance to enable the development of effective therapeutic approaches. We observed up regulation of the anti-apoptotic protein c-FLIP and its up stream regulators including receptor tyrosine kinase RON and transcription factor NFκB (p65) in tumors obtained from metastatic prostate cancer patients. We also observed significant downregulation of these molecules in prostate tumors isolated from patients treated with docetaxel as first line therapy. Further, we identified the over the counter anti-inflammatory agent, Nexrutinesuppresses c-FLIP protein levels and expression in androgen-independent prostate cancer cells (PC-3). Remarkably, the observed decreased levels of c-FLIP were further reduced in combination with docetaxel. Transient expression assays coupled with electrophoretic mobility shift and DNA affinity protein assay revealed that Nexrutine and docetaxel suppresses c-FLIP promoter activity by preventing p65 binding. Notably, Nexrutine in combination with docetaxel abolished binding of p65 to the c-FLIP promoter sequence containing NFκB binding sites. Biologically, these alterations resulted in reducedgrowth of PC-3 cells. Taken together, these observations suggest the utility of RON, p65 and c-FLIP as potential markers to predict response to docetaxel treatment. Furthermore, our results also identified Nexrutine as an agent to potentiate the therapeutic response of docetaxel by suppressing activation of c-FLIP and its upstream regulators. This article is protected by copyright. All rights reserved.

Print Options

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 2008-2022 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.