Notching cancer stem cells

A few days ago I made some connections between a couple of items that I read online and an "old" post of mine. I am still in the "could this possibly be true?!" stage (more like a daze, really). At any rate, I will anticipate a few of my findings today, even though I have only just begun my research on this topic and still have a few things up my sleeve. But let me proceed in chronological order.
On April 12th and then on April 14th, I read two Science Daily articles ( and 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 ( 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.  


  1. I’m lost. You write: ‘adult bone marrow stem cells do not require Notch signals’. What are adult bone marrow stem cells? Does this mean that young bone marrow stem cells DO require Notch signals? Are we killing the young cells with curcumin?
    As I’ve told I’m completely lost. And I don’t like the feeling 🙂

  2. I think they are called “adult” simply to distinguish them from “embryonic” stem cells.
    This stem cell topic isn’t an easy one for me, either (now, why didn’t I pick BIOLOGY at university???), but this website may help clear up your doubts:
    No worries, Sherlock, curcumin is doing only good things for us…if it weren’t, I would stop taking it immediately and I’d warn everyone. Davvero!
    Margaret 🙂

  3. If you take curcumin and want to get the most out of it that it with black pepper or piperine. I think 20mgs makes the bioavailibility of curcumin 2000% better. Piperine inhibits the degradation of curcumin which is typically metabolized very fast by your enzymes.

    Notch, Wnt and Hh. All important embryonic and cancer pathways.

  4. Whoa now! But what about the stem cells in all the other tissues aside from bone marrow?! Has it been proved that they are not affected either?

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