[Mike F]

New study on curcumin

by Mike F on Wed Jul 11, 2018 11:37 am

I just ran across this study today on a possible mechanism for curcumin in cancer treatment. The authors have shown that it affects the 26S proteosome, which is the same cellular unit that Velcade and Kyprolis work on. Even the abstract is pretty dense as far as the biochemistry goes, but I thought I'd pass is alont. Looks like a good reason to take it if you got it.

The abstract is below:

Banerjee, et. al., Ancient drug curcumin impedes 26S proteasome activity by direct inhibition of dual-specificity tyrosine-regulated kinase 2, Proc Natl Acad Sci U S A. 2018 Jul 9. pii: 201806797. doi: 10.1073

Curcumin, the active ingredient in Curcuma longa, has been in medicinal use since ancient times. However, the therapeutic targets and signaling cascades modulated by curcumin have been enigmatic despite extensive research. Here we identify dual-specificity tyrosine-regulated kinase 2 (DYRK2), a positive regulator of the 26S proteasome, as a direct target of curcumin. Curcumin occupies the ATP-binding pocket of DYRK2 in the cocrystal structure, and it potently and specifically inhibits DYRK2 over 139 other kinases tested in vitro. As a result, curcumin diminishes DYRK2-mediated 26S proteasome phosphorylation in cells, leading to reduced proteasome activity and impaired cell proliferation. Interestingly, curcumin synergizes with the therapeutic proteasome inhibitor carfilzomib to induce apoptosis in a variety of proteasome-addicted cancer cells, while this drug combination exhibits modest to no cytotoxicity to noncancerous cells. In a breast cancer xenograft model, curcumin treatment significantly reduces tumor burden in immunocompromised mice, showing a similar antitumor effect as CRISPR/Cas9-mediated DYRK2 depletion. These results reveal an unexpected role of curcumin in DYRK2-proteasome inhibition and provide a proof-of-concept that pharmacological manipulation of proteasome regulators may offer new opportunities for anticancer treatment.

[Multibilly]

Re: New study on curcumin

by Multibilly on Wed Jul 11, 2018 10:01 pm

Thanks for posting this Mike!

Here's the entire article:

http://www.pnas.org/content/early/2018/07/05/1806797115

The article also references quite a few tests on laboratory myeloma cell lines and mice. The closing paragraph in the discussion section is also worth noting:

Curcumin has been one of the most controversial yet extensively studied natural products over the past three decades, having been implicated in a wide range of diseases, often with contradictory results reported by various groups worldwide (6). Considering the poor pharmacokinetics/pharmacodynamics (PK/PD) of curcumin, there is an unresolved debate on curcumin treatment as a viable therapeutic option (6). Our current work establishes curcumin not only as an excellent research tool for DYRK2 inhibition, but also as a potential therapeutic possibility. Derivatives of curcumin with improved PK/PD could be viable treatment options especially for proteasome-dependent highly refractory TNBC or multiple myeloma in the future. With respect to the vast body of literature on potential targets of curcumin, we do not claim inhibition of the DYRK2–proteasome axis as the only possible mechanism of action of curcumin; nevertheless, we have conclusively established that impairment of proteasome activity by DYRK2 inhibition is a major mechanism of action for curcumin in the context of the alleviation of proteasome-dependent neoplastic malignancies.

[jganter]

Re: New study on curcumin

by jganter on Wed Sep 19, 2018 1:15 pm

When I was taking 8 grams/day based on the Golombick et al. study described in this Beacon news article and mentioned in this forum thread, I worried about toxicity. While toxicity seems to be rare, the report I reference below is interesting in that it describes one case of liver toxicity associated with curcumin (turmeric) supplementation.

I took 8 grams/day for a few months and it did not seem to have any effect on my numbers. But my lambda was already in the hundreds, so it was late in the game. My situation is anecdotal and I don't think it is an argument against taking curcumin during MGUS. It is one of the few things you can do.

Reference:

Lukefahr, AL, et al., "Drug-induced autoimmune hepatitis associated with turmeric dietary supplement use," BMJ Case Reports, Sep 10, 2018 (abstract)

Abstract:

"Turmeric dietary supplement sales, which accounted for US$69 million in spending in 2016, have been increasing exponentially in the USA, making this one of the most popular botanical supplements sold in the USA. Herbal supplement use, which is generally regarded as safe by consumers, is not usually reported to healthcare providers. We reported here on a case of autoimmune hepatitis, occurring in a 71-year-old woman taking turmeric dietary supplements for the maintenance of cardiovascular health, which resolved rapidly following discontinuation of the turmeric supplements. Of particular note, turmeric use was not documented in the patient’s medical records and the potential causative role of the turmeric supplementation was ultimately identified by the patient rather than the healthcare providers. To our knowledge, this is the first documented report of turmeric supplement-induced autoimmune hepatitis."

[Eileenk]

Re: New study on curcumin

by Eileenk on Tue Sep 25, 2018 1:33 pm

Thanks for posting this study, I find it encouraging.

I have just hit my one year anniversary being diagnosed with smoldering multiple myeloma at 30-40% in the bone marrow. I was lucky not to have any of the bad FISH results. I started taking 8 grams of longvida curcumin since the very beginning along with some other supplements recommended by my integrative doctor. I see a myeloma specialist and an integrative doctor.

I just had my appointment and overall my numbers have been stable. I consider that a win! It is interesting as every 3 months I panic before each blood draw and at times we needed to add sooner draws if something looked off, but in the end with the highs and lows it seems ok.

I do credit my stability with the supplements, exercise routine, clean eating and getting enough rest. I am currently in a Crohn's flare, but I try to remember it can always be worse.

Eileen