Curcumin, ion channels and cell membranes

March 9 2009 post. Hehe, I love it. Curcumin, the disciplinarian! According to yesterday’s Science Daily newsletter (see http://tinyurl.com/cgxhcp), a recent study shows how curcumin actually works inside the body, at the cell membrane level. Extraordinary. Curcumin actually gets inside our cell membranes, making them more orderly, thus improving the cells’ resistance to infection and malignancy. It acts like a disciplinarian: “behave or else…!!!”

 

My favourite quote from the article: The [cell] membrane goes from being crazy and floppy to being more disciplined and ordered, so that information flow through it can be controlled […]. Amazing, huh? 

 

Interesting titbit: the lead scientist in this project, Prof. Ramamoorthy, As a child in India, […] was given turmeric-laced milk to drink when he had a cold, and […] breathed steam infused with turmeric to relieve congestion.

 

I asked Sherlock if she could get her hands on the full study, but a quick glance at the abstract (http://tinyurl.com/atknp7) tells me that it may be way over my head. I will give it a whirl, though. One important excerpt from the abstract: curcumin has a strong effect on membrane structure at low concentrations. At low concentrations…hmmm, this might help explain a few things…

UPDATE. March 17 2009 post. Sherlock (grazie!) sent me the full curcumin/cell membrane study (abstract: http://tinyurl.com/atknp7), the one that I mentioned in my March 9 2009 post. What was I thinking? What do I know about gramicidin channels of varying lengths and bilayer deformations? Er, not much, I’m afraid…

UPDATE March 18 2009 post. This is a sort of continuation of yesterday’s post. In his comment, Peter asked an excellent question…my answer is that he is right, that these studies may not help us in practical terms right now, but they do point to the possibility that there is more to the curcumin picture than its well-documented poor bioavailability (when administered orally). The evidence that there may be other mechanisms at work seems to be accumulating…that is, unless I have completely misunderstood the studies that I have been reading recently!

 

The 2006 study (abstract: http://tinyurl.com/awyvv9) that I want to discuss today was sent to me recently by a friend (grazie!). It examines the link between the anticancer effects of dietary compounds and ion channels, which are membrane-bound proteins […] that are present on the surface of various cancer cells and tissues. Heh, and I thought cell membranes were difficult!

 

The activity of these ion channels is essential, it appears, for the progression of cancer…and metastasis. When certain ion channels (VPSCs, or voltage-gated sodium channels) are upregulated while others (VGPCs, or voltage-gated potassium channels…er, don’t ask!) are downregulated, in fact, cancer cell membranes get all excited, in line with such cells’ ‘hyperactive’ behaviour. The activity of ion channels has been found to control/enhance a variety of cellular behaviours that would be involved in the metastatic cascade. Oh boy.

 

The researchers therefore suggest that ion channels may be a major target for the anti-cancer effects of some natural compounds. By the way, an explanation of ion channels can be found at “Ion channels for beginners”: http://tinyurl.com/cae5b6 (see “Things ion channels do,” in particular). And the term “voltage-gated” is explained here: http://tinyurl.com/2lpqmo

 

At any rate, the main point is that the researchers set out to see if ion channels could be affected by a few well-known anticancer dietary compounds. What they discovered is significant, since, as I understand matters, when ion channels are affected, the various processes that lead to cancer progression/mestastasis are essentially stopped.

 

Well, as it turns out, resveratrol affects ion channel activity, thus reducing the excitability of metastatic cancer cells. So does curcumin, even though more evidence is needed for the latter, according to the study. The list of ion channel-affecting substances goes on: capsaicin, genistein, ginseng…ah, also omega 3 PUFAs and zinc. In fact, thanks to this study, genistein moved to the top of my to-be-tested supplement list.

 

My own ramblings. Okay, we know that very little curcumin ends up in the bloodstream, plus a lot of it gets transformed into metabolites that may not be as powerful as the original stuff (although that is an unresolved question, as we have seen in previous posts)…but just yesterday we learned that curcumin affects cell membranes…and today we find out that curcumin most likely affects ion channels, which are involved in cancer progression and metastasis. Well, the only possible conclusion, in my view, is that curcumin and other poorly bioavailable substances may work in ways that have yet to be explored. And this is all very encouraging to me, an enthusiastic curcumin-taker with smoldering myeloma…

But…I tried. And, incredibly!, I managed to glean a few pearls. As follows.

 

Despite intense interest in the physiological effects of curcumin, a general mechanism for its action has not been identified. Studies of curcumin have shown that it influences structurally unrelated membrane proteins across several signaling pathways.

 

So the business about curcumin possibly affecting membranes had been hypothesized in previous studies. In a moment of utter madness, I actually glanced at a couple. A 2008 study (see http://tinyurl.com/buza49) suggested that curcumin affects the function of membrane proteins. But these changes had not been studied in detail until Prof. Ramamoorthy and his group examined them with solid-state nuclear magnetic resonance techniques (see: http://tinyurl.com/cvvzb3).

 

After trying to make heads or tails of quadrupolar coupling, acyl chains, anionic amphiphiles and all the other incomprehensible (to me) thingies mentioned in Prof. Ramamoorthy’s report, I gave up and jumped directly to the Discussion…parts of it were beyond my comprehension even after several read-throughs. But a few things were fairly clear.

 

An interesting suggestion concerns liposomal curcumin: It has also been reported that liposome-encapsulated curcumin has greater bioavailability and in vivo efficiency. Our results suggest that the incorporation of curcumin into liposomes strongly enhances the stability of curcumin and may have a strong impact on the demonstrated greater effectiveness of liposomal curcumin.

 

Curcumin stuck inside a liposome (see: http://en.wikipedia.org/wiki/Liposome)….a simple (?) solution that sounds better (to me) than the enteric-coated capsule idea.

 

Important excerpt: Cancer cells treated with curcumin display some features typical of apoptotic cell death […]. However, other features of curcumin-induced cytoxicity […] are not typical of standard apoptosis and point to a direct action of curcumin on the membrane as the initial step in the cytotoxic effect of curcumin on cancer cells. Fascinating.  

 

In conclusion, this 2009 study is the first to detail the real and dramatic changes caused by curcumin in cell membranes. I found most of it difficult or even impossible to interpret, but the parts that suggest that curcumin’s anticancer activity begins at the atomic level might help explain why this yellow-orange powder keeps some of us stable in spite of its well-documented poor bioavailability. Of course, given my lack of scientific training, this is just my own guesswork!

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