Apigenin

Most recent post first.

April 20 2012: A write-up on parsley (good source of apigenin): http://goo.gl/Ejt58 And here is a bit of info on parsley “safety”(source: Drugs.com):http://goo.gl/Uka2H 

April 17 2012 postAt the beginning of April, Vaxil BioTherapeutics released the interim results from its Phase I and II vaccine trial in multiple myeloma patients. The full shebang is available online for free, so I don’t need to do much…commenting (though I probably will, hehe): http://goo.gl/ec1ZI

The vaccine, called ImMucin, targets something called MUC1 (the “Muc” in “ImMucin”!) = a gene that can cause cancer also known as an “oncoprotein.” As we can read in the above-mentioned press release, MUC1 is present in 90% of all tumors. OF ALL TUMORS. Myeloma, too, of course. Myeloma cells thrive on MUC1…but when this oncoprotein is blocked, they all die (see this Dana Farber 2012 study, e.g.: http://goo.gl/zmvNR). A no-brainer, eh…

I’ve already written about this vaccine (see my January 19 2012 “apigenin” post:http://goo.gl/X01ht), mainly because apigenin—a natural compound found mainly in celery and parsley—also inhibits MUC1…How about that? So hey, this is something we can all do…I mean, while waiting for more info to be released, it can’t hurt to increase our intake of celery and other apigenin-containing foods (but please be careful about eating too much parsley, which could be toxic in high doses…My above-mentioned post includes a bunch of warnings, so please have a look at it first…). 

Back to the Vaxil press release now. Only seven multiple myeloma patients have thus far been treated with the ImMucin vaccine. And here are the preliminary results: the vaccine has a very high safety profile. No side effects were observed with the exception of minor local irritation which all resolved themselves within 24 hours without the need for any additional treatment or medical intervention. Sounds good…

And, after only being given 2-4 doses (out of 12), all the patients had a robust and specific immune response. Indeed, some of the patients’ cancer markers stabilized or even decreased. And three out of seven patients are in complete response now. No news on how the four others are doing, though. But this is a press release whose main goal seems to be that of announcing a company merger, so I suppose the lack of medical details is to be expected.

Now here is a really interesting…and important titbit: Firstly, ImMucin can be offered to a very wide section of the population with no need for complicated and expensive personalization or prior selection based on the patient’s immune system. Second, ImMucin has the ability that may enable it to cope with the tendency of the tumor to evade the immune response and develop resistance to treatment. Aha!

Well, that’s what we know so far. It looks very good on paper, but of course we have to keep in mind that the vaccine producers themselves are releasing their own data. So before getting too excited, I’d like to see some independent trial data. Still…

Fingers crossed! :)

January 19 2012: Back in mid November, a blog reader (thanks, J!) posted a link on my blog’s Facebook Page about the development of a cancer vaccine called ImMucin, which, and here’s the exciting part!, was being tested in clinical trials on patients with multiple myeloma. Very exciting news. 

Now, I’d known for a while that a vaccine was in the works. But the 2005 clinical trial testing the vaccine (same thing, same company etc.) had been “withdrawn prior to enrollment”…no explanations given. It might have been a simple sort of bureaucratic hiccup…I mean, they might simply have run out of funds or whatnot. But, lacking an explanation, I stopped following this “case.” 

And that is why I’m very grateful to J for bringing the vaccine to my attention again. I noticed that this second trial (still recruiting, btw) has added something to the mix, something called “recombinant human granulocyte-monocyte colony stimulating factor.” Drat, I don’t have the time right now to check on that…oh well. But it left a question in my mind, since the first trial was only going to test ImMucin by itself…hmmm…

I’m also verrrry grateful to another blog reader, L, for pulling together a whole bunch of links for me. Back in November, however, I have to confess that I was overwhelmed, so I postponed writing a post on this topic until I had more time to check out all L’s links and do more research. Of course, time passed, life got busy and eventually, well, I forgot about it (my deepest apologies both to J and L). 

Until today.

Today a third (!) blog reader sent me a link providing an update on the clinical trial:http://goo.gl/O4kRc (you can also check the Clinical Trials website: http://goo.gl/uNyMs). Here’s an interesting excerpt: The new vaccine works by activating the immune system by “training” T-cells to search and destroy cells with the MUC1 molecule, typically found only on cancer cells. More than 90% of common solid tumor cancers bear the MUC1 molecule, as well as many non-solid tumors, including lymphoma, leukemia and multiple myeloma.  

Okay, so we know that the vaccine blocks a thingy called MUC1. Well, back in November, my above-mentioned blog reader L had the absolutely brilliant idea of checking to see if there were any natural MUC1 blockers. Success! Wonderful L found a study (full text available online: http://goo.gl/3b0yn) showing that apigenin blocks MUC1.

I’ve written a few posts about apigenin, a compound that can be found mainly in parsley but also in other foods and herbs (do a Search of my blog for “apigenin”). The most important one would be my August 30 2011 post in which I reported about a Chinese study showing that apigenin kills myeloma cells on its own (full text available online for free: http://goo.gl/Rqs02).

L also sent me the link to a 2009 study linking MUC1 to the NF-kappaB pathway, which is one of the main bad guys in myeloma: http://goo.gl/RJ3JI As the study’s title suggests, MUC1 activates NF-kappaB, which is clearly BAD. The great news therefore is: if we can stop MUC1, we can block NF-kappaB, too. Theoretically. 

So, given all this great info about apigenin’s dual activity (= blocking MUC1 AND killing myeloma cells), why wait until 2017 for the vaccine to be available on the market? Why can’t some of us go ahead and increase our daily intake of apigenin? I’m referring to those of us who aren’t on any chemo or other drugs whose activity might be hindered by apigenin. And here I must tell you this: before imbibing huge quantities of apigenin via parsley or a supplement, please keep in mind that it might possibly interfere with the drugs you are taking. Wonderful L sent me a list that you can check out: http://goo.gl/p5MFK She also pointed out that parsley is loaded with vitamin K, which can interfere with coumadin or blood-thinning meds.

Bottom line: do your research…ask your doctors before taking anything…and please be careful. 

L also found out that dry parsley actually contains a higher amount of apigenin than fresh parsley. She calculated that 2.4 grams of dried parsley has the same amount of apigenin (300 mg) as 100 grams of fresh parsley

She didn’t stop there. She went into her kitchen and did some measuring for us (love that!). She calculated that each gram of dried parsley yields 135 mg of apigenin. And one gram of dried parsley = two level teaspoons. So that seems to be an easy way to get more apigenin into our body. I mean, two teaspoons of dried parsley added to a glass of water (L tried it and reported that the taste was okay) will give us 135 mg of apigenin, based on L’s calculations. 

My own very quick bit of research this morning led me to a Chinese study on EGCG and the wayward MUC1 protein: http://goo.gl/uCs0b So yay, we can add another readily available item to our natural, anti-MUC1 list.  

Well, this post is not exhaustive by any means, but it gives us a start, at least…

August 30 2011 post. 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)…

December 6 2008 post. In my November 30th post I had a look at chemoresistance. Well, it just so happens that a few days ago, in a rather vain attempt to catch up on my Science Daily readings, I came across a bit of info (see http://tinyurl.com/56qhxh) that might be particularly useful to those doing chemo right now.

A recent study shows that apigenin, a naturally occurring dietary agent found in vegetables and fruit, can make cancer cells more susceptible to chemotherapy.

Here’s what happens: apigenin apparently localizes tumor suppressor p53, a protein, in the cell nucleus – a necessary step for killing the cell that results in some tumor cells responding to chemotherapy. […] In many cancers, p53 is rendered inactive by a process called cytoplasmic sequestration. Apigenin is able to activate p53 and transport it into the nucleus, resulting in a stop to cell growth and cell death. Now wait a sec. Why wouldn’t this phenomenon also help those of us who are not doing chemotherapy? Well, actually, I guess that would be implied in the researchers’ recommendation that fruit and veggies be included in everyone’s diet to prevent the development of cancer.

So where do we find apigenin? For the most part, in fruit (including apples, cherries, grapes), vegetables (including parsley, artichoke, basil, celery), nuts and plant-derived beverages (including tea and wine). It has been shown by researchers to have growth inhibitory properties in several cancer lines, including breast, colon, skin, thyroid and leukemia cells. It has also been shown to inhibit pancreatic cancer cell proliferation. Thumbs up!

If you do a search for apigenin on my blog, you will find my August 8 2008 post, reporting that this flavonoid doesn’t inhibit Bortezomib, which of course is a good thing for those who are on Velcade.

I did a quick online search on apigenin. Lots of interesting stuff came up, including a 2004 study (http://tinyurl.com/5o4lhw) on rats, which concludes that our body may be able to accumulate apigenin because it is metabolized, absorbed and eliminated slowly. So slowly, in fact, that apigenin was found in the rats’ blood nine days after administration. Incredible, huh? By the way, according to this study, apigenin can also be found in rosemary and camomile, and in honey, fennel and wheat germ.

In this November 2008 study (http://tinyurl.com/5sq5qt), we can read that apigenin inhibits NF-kappaB and also the molecules regulated by this transcription factor, such as Bcl-x (aha!) but not Bcl-2. It also inhibits COX-2. This is very good news for celery fans.

I haven’t been that interested in apigenin because, to my knowledge, there are no specific studies on apigenin and myeloma. But from now on I will try to keep half an eye on it.

Apigenin and leukemia: http://tinyurl.com/6hfgdk

Apigenin and ALL: http://tinyurl.com/5be38e

Apigenin and ovarian cancer: http://tinyurl.com/6qfooo

Apigenin and pancreatic cancer: http://tinyurl.com/6p3k9o

Apigenin and breast cancer: http://tinyurl.com/5qtva2

Apigenin and neuroblastoma: http://tinyurl.com/5ldg8o

The list goes on…

8 thoughts on “Apigenin

  1. arie arieli

    Thank you Margaret for the information about Apigenin.
    A very short search on the web shows that Apigenin can be found in lots of herbs.
    I did’nt get yet into the realm of essential oils
    but as we are dealing with a crystaline substance
    I do’nt put much hope in this direction.
    My computer and internet connection are very slow so I leave the indepth search for those of you better equiped.
    a partial list of herbs containing Apigenin:
    Chammomile,Rosemary ,Green tea ,Hops,Oregano
    and Dandelion.
    Some of them cause Apoptosis in more than one way,
    and all of them have some side effects and contraindication if taken in megadoses.
    what’s nice is the veraiety which enables us to take them in some cyclic way and avoid the side effects that come with long term use of one substance in high dose .
    I surely intend to try those herbs in parallel with my front line C3 Curcumine,Resveratrol,Omega3,Green Tea.

    Reply
  2. Ron

    Has anyone who tried or is using apigenin supplement or parsley noticed any difference in markers or how they feel with this supplement.
    Thanks
    Ron

    Reply
  3. Diane A.

    I took a little parsley oil and garlic oil capsule daily for months and months. I started to be quite clumsy. The day I hurt myself four times and was wearing three band aids, I read too much parsley can affect one’s balance.

    I stopped taking it last week and have my spatial balance back. Huzzah! But the oven burn on my arm is still healing.

    Reply
  4. Andrea

    I use fresh parsley (organic) as much as possible. I throw handfuls of it (stems&all) into soups, salads, dressings, everything…I have been doing this for over a month and while I don’t yet know if this will influence markers, I have not had any adverse reactions.
    Food tastes better too!

    Reply
  5. Ron

    There is also another group, the Mayo Clinic division in Arizona in conjunction with researcher at University of Georgia working on a vaccine based on MUC1 similar to Vaxil product. Google and utube muc1 cancer/myeloma to see researcher interviews.

    Reply
  6. Ronald Sanders

    Collon, Have tried the Swanson product and as with most isolated products I questioned the ability to absorb. Talked to researcher and though no studies have been done on isolated apigenin he thought the apigenin in parsley would be absorbed better since it was attached to a carbohydrate. Parsley also contains other anti cancer compounds which can’t hurt. I think t[his is also the reason studies show turmeric benefits although curcumin is a main active ingredient andis difficult to absorb in the isolated state. By the way,new studies out of Ohio State on apigenin positive for cancer and heart conditions.

    Reply

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