Andrographolide and parthenolide kill myeloma stem cells

My andrographolide-researching blog reader also sent me the link to a 2011 U.S. study on the effects of parthenolide (remember PTH? Remember DMAPT? Yeah, I haven’t written about it in a long time…making mental notes right now…) and andrographolide on myeloma stem cells: goo.gl/3e6Nk5

That’s right…on MYELOMA STEM CELLS.

Problem: only the abstract is available for free online. With the help of a fab friend, however, I was able to read the full study, but I have to be careful about copyright issues, even though it irks me that you have to pay for studies that could be of vital importance to us. Of course, I DO understand that journals need to survive. And so…well, let’s have a look, without going into too much detail. Compromises…

Incidentally, this is the first study discussing “a natural product with anti-CSC activity in myeloma” (CSC = cancer stem cell).

As we all know, the main problem with myeloma is RELAPSE. Relapse is caused by the tough myeloma stem cells, the cells that can clone themselves, the really bad thugs that escape being killed by chemotherapy. The chemo drugs used in myeloma target the general plasma cell population, that is, the cells that cannot reproduce themselves, BUT they are NOT able to eliminate our myeloma stem cells. So no matter how many chemo bombs we throw at our myeloma, there will always be a handful of nasty ruffians in hiding, ready to come out and start proliferating again at some point.

This study shows that parthenolide AND andrographolide do just that: they go after the ruffians. The abstract calls them two “potent anti-MM-CSC agents.”

Potent…I like that!

Okay, I’m going to see if I can extract some gems from the full study.

As we’ve seen, it’s not enough to target the circulating plasma cells. If we want to get rid of the myeloma weed, we must go after the stem cells, the “clone troopers” (Star Wars, anyone? 😉 No, I’m not really a fan, but I do remember that expression…). The only way to prevent relapses is to kill the cloners!

Parthenolide is the first extract to be discussed. In addition to being a powerful NF-kappaB inhibitor, parthenolide (PTH from now on) kills the stem cells of myeloma and of acute myelogenous leukemia, without killing the normal hematopoietic cells, the good guys, which produce red/white blood cells and platelets. One big problem has been PTH’s has low solubility in water (but remember DMAPT? It’s water soluble… but these researchers don’t mention DMAPT, except in their References…anyway…).

Andrographolide (AGR from now on) hasn’t been studied as much as PTH. However, it’s more soluble in water compared to PTH. That is very good news…

The researchers point out that melphalan and bortezomib “are not curative” (their words, not mine), because they don’t target the MM stem cells.

But, they add, that’s what PTH and AGR do…

One of the coolest things about this study, IMO, is that the researchers used a 3-D tissue culture of rBM, which is basically a reconstruction of a bone marrow microenvironment (rBM stands for reconstructed bone marrow). They also used 2-D cell cultures. They were able to confirm that the main target of PTH and AGR were the myeloma stem cells.

Clearly, more research is needed…more testing…but I’d say that this study shows how promising these two extracts are. We need to rip out the myeloma weeds…without harming ourselves in the process…

Testing promising natural extracts is a step in the right direction.

Are our official myeloma organizations going to do something about this very important study??? C’mon!!!!!!

A new anti-myeloma substance: andrographolide

A blog friend (thank you!!!) sent me the link to a few studies on andrographolide, extracted from a medicinal plant called Andrographis paniculate, native to South Asian countries and also known as the “king of bitters.” The leaves and underground stems of this plant are used for about a million purposes: to prevent and treat colds and the flu, to treat digestive disorders (diarrhea, colic, stomach pain and so on), liver conditions (jaundice, liver damage caused by medications), infections (all sorts, from pneumonia to rabies, even HIV/AIDS), and skin conditions.

The list is seemingly endless and even includes snake bites, loss of appetite, kidney problems, hemorrhoids, worms (ugh). It has antibacterial, anti-inflammatory, antiviral, anti-tumor, anti-fungal, and immune regulatory, properties. It also protects the gallbladder and the liver. Oh, and apparently it is good for the heart, too!

But the main reason I’m writing about this seemingly amazing substance today is because it has ANTI-MYELOMA properties. What I really like about this new (new to me!) substance is its “low toxicity and low cost.” 

Luckily for us, the main andrographolide-MM study, published in 2015, is available for free online, so you can read it, too. The whole shebang can be found here: goo.gl/Z9CaVF

Incidentally, this is the first study to discuss the effect of andrographolide on myeloma cells…

According to the abstract, these two Chinese researchers showed that andrographolide reduced the proliferation of MM cells and increased their death rate (apoptosis) by inhibiting the NF-kappaB pathway that we’ve learned so much about in all these years.

Results: as mentioned in the abstract: 1. andrographolide blocks the proliferation of myeloma cells; 2. It also KILLS them (“induces apoptosis”). And that’s really all we need to know, although the study offers other important details, too.

Let’s look at one of them, since it is connected to an item of MUCH interest that pops up later in the study: andrographolide reduces the levels of the TLR4 protein and of the NF-kappa B pathway in myeloma cells.

Discussion: andrographolide also inhibits angiogenesis, which is so important for the survival and wellbeing of myeloma cells, so that’s good to know, too.

Now we get to the above-mentioned importance of the TLR4 protein. TLR4 is apparently involved, not in a good way!!!, with a tumor’s microenvironment and has a lot of power over immune cells. So, if its activity can be blocked, that’s very good news. With andrographolide, this can be accomplished…

I mentioned TLR4 in one of my earliest posts, written in 2007: TLRs, or toll-like receptors, play a key role in the immune system. Back then, I was interested in the fact that TLR4 is inhibited by…yes…curcumin. This all makes sense, eh?

Anyway, definitely a very interesting substance. I’ll be looking at more studies on this topic in the next few days. I think it might deserve more than just ONE post. Right now it’s at the top of my list of stuff I intend to test…