I have already written a few posts about apigenin, a common flavonoid found in celery and parsley (see http://margaret.healthblogs.org/antioxidants-and-chemotherapy/chemoresistance-apigenin/). When I first began reading the apigenin studies, I just knew that this compound would kill myeloma cells, too. But I wasn’t able to find a specific apigenin-myeloma study. Until today, that is…

A Chinese study on this very topic was published just yesterday in “Molecular Cancer.” The provisional PDF, yes the full study, is available online: http://goo.gl/CyO3Y. Super!!!

As we can read in “Results,” this group of researchers found that apigenin killed myeloma cells but NOT normal, healthy cells. The gist of the headache-causing paragraph discussing STAT3 and NF-kappaB is that apigenin was found to inhibit a rather impressive bunch of signalling processes and evil proteins that are all involved in myeloma cell survival. In the end, all the inhibiting and downregulating by apigenin inexorably led to the DEATH of myeloma cells. 🙂

Another thing: apigenin helped two drugs (geldanamycin and vorinostat) deplete what the researchers called Hsp90 clients. Now, here I would like to digress for a second on the topic of Hsp90, known also as heat shock protein 90.

This is one of the most common proteins you can find in a cell. And, as its name suggests, it protects cells that are exposed to high temperatures and stress. When that happens…well, let’s try to explain it with a Cape Cod (Massachusetts) summer scenario. The Cape has 215,000 year-round residents. In summer, though, when the summer people arrive, the Cape’s population doubles. Well, that’s essentially what happens with the Hsp90 “clients.” When these “clients” enter a myeloma cell, that is, they go nuts and start proliferating like mad, doubling their normal numbers. Now, I don’t mean to sound negative towards tourists (Cape Cod really needs ’em!!!)…I just needed an easy-to-understand image that would help understand how this process works…and the doubled population of the Cape came to mind. That’s all! 

So, in conclusion (of this part!), multiple myeloma cells, as well as other cancer cells, contain more Hsp90 than normal cells, probably because they are subjected to more types of stress (than normal cells, I mean), such as low levels of oxygen blablabla…

And so Hsp90 has become a cancer treatment target. If you are interested in the Hsp90 topic, have a look at http://goo.gl/IDc0z Please read what Dr. Paul Richardson had to say about the halting of this trial…very interesting. As usual, the patients’ best interests are less important than big pharma profits…

But let’s get back to the apigenin-myeloma study. I liked it a lot also because it explains the meaning of many acronyms and describes their activities, instead of assuming that readers will automatically know all this stuff…For example, see how the authors discuss Cdc37, which is one of those pesky Hsp90 folks that is, quelle surprise (not!), overexpressed in myeloma. “Overexpressed” is like Cape Cod traffic in summer…or like traffic in Florence (Italy) all year round (except in August, when Florentines are on holiday)… 😉

At the end of page 4 we get to a description of apigenin, which, we are told, is abundant in common fruits and vegetables. It stops MM cells from proliferating…but the best bit of news is that it exterminates them once and for all, by suppressing CK2 as well as halting the nefarious activities of Cdc37 and the Hsp30 “chaperones.”

Skip skip skip to bottom of page 10, where we find some “Results,” which simply confirm the death of two important myeloma cell lines—U266 and RPMI 8226. The effects of apigenin on those two cell lines was dose-dependent, which means that the effects change if and when the dose is changed…For example, if you take 500 milligrams of curcumin, you most likely will not notice any improvement in your cancer markers. If, however, you increase that dose to 8000 mg, you most likely will notice a change. So curcumin’s effects are also dose-dependent…

Back to the study. Apigenin also inhibited what are called antiapoptotic proteins, such as Mcl-1, Bcl-xL and survivin (I’ve written about these in several posts…do a “Search” of my blog if you want details; use the Search box on the right). These are some of myeloma’s best buddies…They help keep myeloma cells alive and well…as do some of the signalling pathways, such as STAT3 and AKT. Well, these buddies and evil pathways are inhibited by apigenin. A note about doses: these studies are in vitro only, so we’re talking about CELLS…So it’s too early to tell what sort of dose might be helpful in humans…

One interesting paragraph has to do with cells donated by (12) MM patients and (5) healthy donors. The cells donated by 11 of the MM patients turned out to be sensitive to apigenin (yaaay!), but those from donor no. 12 only showed a slight growth inhibition. So they weren’t much affected by apigenin (the authors discuss this later on in the study…and say that they are now trying to figure out why this occurred). The healthy donor cells were unaffected by apigenin, which is great, of course…Like curcumin, apigenin therefore seems to be able to distinguish between cancer/myeloma and normal cells. Super duper…

The “Discussion” part suggests that apigenin’s anticancer activity may be caused by its strong proteasome inhibition activity. Earlier in the study we’d learned that apigenin inhibits proteasomes…just like Velcade and curcumin. Interesting…

Important: the researchers mention EGCG and resveratrol as two other CK2-inhibitors, but I would like to mention curcumin, too. Oh, and of course, curcumin inhibits Hsp90, too…almost goes without saying, by now!!! 😉

There follows an interesting discussion concerning the members of the Bcl family (=evil, mafia-like protectors of myeloma cells)…and Mcl-1, another noxious protein that becomes overexpressed in myeloma cells. When Mcl-1 is downregulated (=calmed down, sort of), myeloma cells die. I would like to note that curcumin also downregulates Mcl-1, although by now that sort of announcement shouldn’t even make us raise an eyebrow… 😉

Good discussion also of how myeloma cells proliferate, the roles of IL-6 and VEGF and so on…

Well okay, what does all this mean, all of this multiple signalling pathway and kinase activity inhibiting stuff? Basically, that it would be a good idea to start eating lots of celery and parsley (though didn’t I read somewhere that huge quantities of parsley can be toxic? So be careful with that one…). Other foods that contain apigenin are rutabagas and also, in smaller amounts: apples, beans, broccoli, cloves, grapes, leeks, onions, tomatoes…hey, and tea and wine!

But mostly, in order, parsley (#1), then celery (#2) and rutabagas (also #2)…