Doing research for a recent post, as frequently happens, I came across an interesting abstract with some hard-to-believe news. My brilliant friend Sherlock (grazie!) kindly sent me the full study, published in the Journal of Biological Chemistry in June 2007. According to the abstract (http://tinyurl.com/3yqzc6), Administration of curcumin to tumor-bearing animals resulted in restoration of progenitor, effecter, and circulating T cells. Curcumin can reinstate our T cells at every stage of their development? No way! (Yes, way). Hmmm, the question arises: why should we care about T cells? Well, if we didn’t have any T cells, we would be like nude mice, yes, the sort used in lab experiments. We would have no way of fighting off disease. T cells, in a nutshell, are crucial players in our immune response to diseased cells.
Let’s take a look at the full study: In order to establish itself, a growing tumor must evade the immune system of the host. This contributes to tumor-induced immune suppression. A growing tumor can evade the proposed immune surveillance by several mechanisms. One of these mechanisms is to kill (induce apoptosis of!) our T cells. Reading on, we learn that Increased oxidative stress because of the growing tumor can be another cause of immune disruptions. Recently, several observations indicate that a chronic inflammatory condition develops in patients with advanced cancer, causing oxidative stress that can shut off immune functions, including those of T and NK cells. Oh, this is not good at all.
Before proceeding, let me just mention that I was confused enough about all these different types of cells that today I looked everything up, from A to Z. I am now in the midst of putting together a brief (!) explanation (?) of a very complex topic. For now, let it suffice that B, T and NK (natural killer) cells are three types of lymphocytes (white blood cells) that originate from hematopoietic stem cells (HSCs), located in the bone marrow. They have different functions, but we don’t need to get into the nitty gritty, yet. If you can’t wait for my explanation, then click on the fabulous link I provide below. Back to the study, now.
A tumour has a negative influence on the production of T cells in the thymus, which is a small organ, located behind the sternum, that produces T cells (the “T” stands for “thymus,” in fact). A tumour causes a massive depletion of both thymic and circulatory T cell populations. Massive depletion of T cells? Yikes. But there is GOOD news. The administration of curcumin brought back thymic CD4+8+, CD4+, and CD8+ cells as well as circulatory effecter CD4+ and CD8+ cells to control level. (CD4 and CD8 are the two main T cell subsets, by the way.) Curcumin brought these cells back to CONTROL level? Well, knock me down with a feather!
Ah, but it gets better. Curcumin protected T cells from being killed by the tumour. When preincubated with curcumin, these cells turned into Superduperfantastic cells, resistant to any tumour attack (sort of like Harry Potter versus Voldemort). In other words, they survived. Oh, sure, this is all happening in vitro. But the researchers experimented with mice, i.e., in vivo, too. Exact same results. They conclude that from aforementioned in vitro and in vivo results, it may be envisaged that curcumin might also protect T cells from a tumor-induced demise in humans. Hey, it’s not every day that I get excited about something called thymic CD4 plus! 😉
My next topic stumped me for hours, it seems, until I came across an absolutely brilliant website that opened up a whole new world for me: the world of relatively easy biology. Itsy bitsy thingies no longer have any secrets for me thanks to John Kimball, a retired biology professor who taught at Tufts and Harvard (I must remember to write him a glowing fan letter). The updated sixth edition of his biology textbook is online (free, too): http://tinyurl.com/57ygj So from now on, if you ever have a doubt about, say, the JAK-STAT pathway, this is the place to go. 😉 Seriously, though, thank you from the bottom of my heart, Prof. Kimball! Everything is crystal clear now. Well…more or less!
Here’s what stumped me: in the curcumin T cell study, I read that tumours downregulate the anti-apoptotic Bcl-2 protein (take my word for it, this is NOT a good thing). But that’s precisely what curcumin does: it downregulates Bcl-2 in myeloma cells. Wait, how could this be? Why is the downregulation of Bcl-2 bad for T cells, good for myeloma cells? Ah, you see, perhaps, had I written out the question, I wouldn’t have spent hours trying to figure it out!
It’s very simple, really. In the case of T cells, in fact, we WANT to have a high level of Bcl-2. In the case of myeloma cells, we don’t. Prof. Kimball’s page on Bcl-2 explains that B cells, like all activated lymphocytes, die a few days after they have had a chance to do their job. This ensures that they do not linger around after the threat has been dealt with and turn their attack against self components. Aging B cells kill themselves by apoptosis. But high levels of the Bcl-2 protein protect the cells from early death by apoptosis. After reading these four sentences, a light went on in my brain: we want T cells to LIVE, but myeloma cells to DIE. Therein lies the difference. Okay, so it took me hours, not minutes, to figure this out, but I am not a biologist, and I didn’t have this wonderful reference text at my fingertips until the latter part of the afternoon.
Well, we have yet another (!) good reason to take curcumin. I can feel my T cells getting more powerful by the second…!
My brain is fried, now, and I need to get off the computer, but will certainly take a second look at this study at some point over the weekend. I would like to end by pointing out that Mary has some good advice for us (see her most recent comment to my December 3rd post). Please go have a look!