Curcumin and Notch Signaling

November 29th 2007 post: a study in this month’s issue of Blood discusses how the Notch signaling pathway protects myeloma cells from apoptosis (death). You can read the abstract here: http://tinyurl.com/ysv9gg After doing an online search for Notch signaling and curcumin, to my surprise (I wonder WHY I am still surprised !), I found that, yes, apparently curcumin inhibits this signaling pathway (important, by the way, for cell to cell communication), see this 2006 abstract on pancreatic cancer cells in vitro: http://tinyurl.com/2cjgpr See also this December 2007 abstract on leukaemic cells: http://tinyurl.com/2hp5z2 I don’t have time to do more research on Notch and curcumin today (busy in other fields ), but it’s always good to come across another good reason to be taking the orange powder! Yeah!

Update April 16 2008 post: On April 12th and then on April 14th, I read two Science Daily articles (http://tinyurl.com/4gcjyc and http://tinyurl.com/5h9jom) that reminded me of a rather superficial post I had written on Notch signalling last fall. That’s what started it.

But first, what is Notch signalling? The Science Daily articles tell us that the Notch pathway sends signals from a cell’s surface membrane into its nucleus. Those signals activate genes that instruct the cell to make proteins that perform various tasks. It helps regulate fetal development and is active in most organ systems throughout a person’s life.

A 2005 Science Daily article (http://tinyurl.com/55xlyx) discusses the role of Notch signalling in the development of T cells: no Notch = no T cells, it would seem. So this is a vital pathway. That is, as long as it doesn’t go whacky. But it does, sometimes.

Abnormal increases in Notch signalling can give rise to T-cell acute lymphoblastic leukaemias, and these increases are present in other cancers as well (myeloma is no exception, hah, figures!): Prior work has shown that increases in signals generated by Notch are important in certain human tumors, particularly some kinds of childhood leukemia, making Notch an attractive target for new cancer therapies.
 
Big problem, though: researchers were concerned that Notch inhibition might have a negative effect on the normal functioning of the healthy stem cells present in the bone marrow. Another “damned if you do, damned if you don’t” situation? Would the inhibition of Notch end up actually destroying the bone marrow? A very scary thought, based on the fact that Many scientists have long assumed that blood-forming stem cells need Notch signals to function properly. But let me note that this sentence was written a couple of years ago. Things have changed in the meantime.
 
A group of researchers from the University of Pennsylvania School of Medicine and colleagues has recently demonstrated that inhibition of Notch signalling will not mess up our healthy stem cells. They discovered that the Notch signaling pathway, which determines the development of many cell types, and is also implicated in some cancers, is not universally essential for the maintenance of stem cells. In fact, adult bone marrow stem cells do not require Notch signals. Super!

The University of Michigan Medical School has therefore begun a “groundbreaking trial” that combines chemotherapy with Notch inhibitors: The aim is to use so-called Notch inhibitors to attack cancer stem cells, the small fraction of stem cells inside a tumor that help it survive and that fuel its growth.

Let me highlight this sentence: Notch inhibitors attack cancer stem cells.

Okay, and here is my bombshell of the day…

Curcumin inhibits Notch signalling.  

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