Replies to post #136298 on Biotech Values

[ilpapa]

I don't remember if this was discussed yesterday, but I have read that curcumin should be combined with piperine to increase bioavailability.

[biomaven0]

>turmeric

One likely mode of action here is inhibition of NF-kappaB via IKKbeta:

The curcumin binds to and prevents an enzyme known as IKK, an inhibitor of kappa ß kinase, from activating a transcription factor called nuclear factor kappa ß (NF?ß), which promotes cancer growth.

http://www.cancer.ucla.edu//Index.aspx?page=644&recordid=507

This relates directly to the interesting paper linked on Sally's blog a few days ago relating to pancreatic cancer - basically there is a feedforward loop involving NF-kappaB:

KrasG12D-Induced IKK2/ß/NF-?B Activation by IL-1a and p62 Feedforward Loops Is Required for Development of Pancreatic Ductal Adenocarcinoma
Summary

Cancer Cell, Volume 21, Issue 1, 105-120, 17 January 2012
Copyright © 2012 Elsevier Inc. All rights reserved.
10.1016/j.ccr.2011.12.006


Authors

Jianhua Ling, Ya'an Kang, Ruiying Zhao, Qianghua Xia, Dung-Fang Lee, Zhe Chang, Jin Li, Bailu Peng, Jason B. Fleming, Huamin Wang, Jinsong Liu, Ihor R. Lemischka, Mien-Chie Hung, Paul J. ChiaoSee Affiliations
Highlights
IKK2/ß-activated NF-?B signaling pathway is required for KrasG12D-induced PDAC
KrasG12D activated IKK2/ß/NF-?B by inducing duel feedforward loops of IL-1a and p62
IL-1a correlates with Kras mutation, NF-?B activation, and poor survival in patients
IL-1a is a therapeutic target to suppress KrasG12D-induced PDAC
Summary

Constitutive Kras and NF-?B activation is identified as signature alterations in pancreatic ductal adenocarcinoma (PDAC). However, how NF-?B is activated in PDAC is not yet understood. Here, we report that pancreas-targeted IKK2/ß inactivation inhibited NF-?B activation and PDAC development in KrasG12D and KrasG12D;Ink4a/ArfF/F mice, demonstrating a mechanistic link between IKK2/ß and KrasG12D in PDAC inception. Our findings reveal that KrasG12D-activated AP-1 induces IL-1a, which, in turn, activates NF-?B and its target genes IL-1a and p62, to initiate IL-1a/p62 feedforward loops for inducing and sustaining NF-?B activity. Furthermore, IL-1a overexpression correlates with Kras mutation, NF-?B activity, and poor survival in PDAC patients. Therefore, our findings demonstrate the mechanism by which IKK2/ß/NF-?B is activated by KrasG12D through dual feedforward loops of IL-1a/p62.

http://www.cell.com/cancer-cell/retrieve/pii/S1535610811004752