curcumin (tumeric) may deplete her2

[Lani]

Curcumin-induced degradation of ErbB2: A role for the E3 ubiquitin ligase CHIP and the Michael reaction acceptor activity of curcumin.

Jung Y, Xu W, Kim H, Ha N, Neckers L.
The Research Institute for Drug Development, College of Pharmacy, Pusan National University, Busan, 609-735, Korea.
We investigated the molecular mechanism underlying curcumin depletion of ErbB2 protein. Curcumin induced ErbB2 ubiquitination but pretreatment with proteasome inhibitors neither prevented curcumin depletion of ErbB2 protein nor further accumulated ubiquitinated ErbB2. Curcumin increased association of endogenous and ectopically expressed CHIP, a chaperone-dependent ubiquitin ligase, with ErbB2. In COS7 cells cotransfected with ErbB2 and various CHIP plasmids followed by curcumin treatment, CHIP-H260Q (a mutant lacking ubiquitin ligase activity) promoted less curcumin-induced ErbB2 ubiquitination than did wild type CHIP, and CHIP-K30A (a mutant incapable of binding Hsp90 and Hsp70) neither associated with ErbB2 nor promoted its ubiquitination. ErbB2 mutants lacking the kinase domain failed to associate with CHIP and were completely resistant to ubiquitination and depletion induced by curcumin. Finally, curcumin's Michael reaction acceptor functionality was required for both covalent association of curcumin with ErbB2 and curcumin-mediated ErbB2 depletion. These data suggest (1) that CHIP-dependent ErbB2 ubiquitination is implicated in curcumin-stimulated ErbB2 depletion, and (2) that covalent modification of ErbB2 by curcumin is the proximal signal which initiates this process.
PMID: 17239458 [PubMed - as supplied by publisher]

[RobinP]

Yes, Lani, I love this article, and I certainly appreciate it. Well, it looks like I will continue to take my tumeric supplements, not just for the benifit of increased her2 degradation but for the cox2 properties too which decreases inflammatory processes like her2!

[RhondaH]

on my salad every day. Take care and God bless.

Rhonda

[eric]

How much is recommended?

[heblaj01]

Eric,
Based on the available data curcumin is very poorly absorbed & is only present in large quantity in the guts when ingested by mouth. ( I never heard of a different mode of administration).
In trials the quantity given is in the order of 8 to 15 grams per day in divided doses. Higher doses may cause GI problems. Addition of Bioperine increases somewhat absorption but does not change much to the relatively short half life (2 to 4 hours) & Bioperine (an extract of pepper) is itself toxic in doses exceeding about 20 mg per day.

[heblaj01]

I don't want to leave a too pessimistic impression from my previous post about the poor absorption of curcumin in spite of the fact that one pharmacologist has come up with dire caculations on bioavailability (http://scienceblogs.com/terrasig/2006/10/curcumin_for_cancer_part_two_1.php)
On the optimistic side is the decision of MD Anderson Cancer Center to undertake clinical trials, although they use the high dosage route to try overcome the lousy absorption. I think they believe that long term supplementation with high doses will cause a small accumulation in the body.It remains to be seen if this will be enough to be therapeutic.
But I assume that they must have made some assessment on the merits of curcumin before starting trials
An other possible positive aspect is a remark by an experimenter trying to reconcile the observed benefits of curcumin for various ailments with the poor bioavailability: he speculated that there maybe some effective curcumin metabolites not yet identified or studied whose absorption might be better that that of curcumin.

On the caution side: curcumin is counterindicated by some oncs in the case of patients taking the Cytoxan (cyclophosphamide) chemo.
An other even less well defined point is the experimental observation that curcumin operates as an antioxidant at low doses (& as an oxidant at high doses). Since absorption is poor this may mean that curcumin may decrease the efficacy of those chemo drugs (such as Cytoxan) which use oxidation as a mode of action.

[AlaskaAngel]

I've been able to "hide" it in a lot of ways in cooking, including cold and hot drinks. I noticed that Silk puts some of it in their eggnog. But I'm going to have to go to the chemist to see what 8 to 15 gm per day amounts to.

A.A.

[eric]

Thanks so much!

[Hopeful]

The test was done in colon cancer cells, but looks interesting. Apparently this "modified curcumin congener" has greater bioavailability: http://clincancerres.aacrjournals.org/cgi/content/abstract/13/4/1269

Hopeful