Chemoresistance, Bcl family, apigenin

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 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 ( 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 (, 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:

Apigenin and ALL:

Apigenin and ovarian cancer:

Apigenin and pancreatic cancer:

Apigenin and breast cancer:

Apigenin and neuroblastoma:

The list goes on…


December 4 2008 post. Quelle coincidence! I wrote a post on the Bcl family just a few days ago (November 30th), and then yesterday I happened to read a Science Daily article on Bcl-2 (see: Fascinating.



The article tells us what we already know, i.e. that the levels of the Bcl-2 gene, cancer’s best friend, are elevated in a majority of human cancers, and Bcl-2 is responsible for cancer cells’ resistance to many chemotherapeutic drugs and radiation. Ok, that is the bad news. But the good news is that all this may change soon, thanks to a new discovery published in “Cancer Cell” in October. Do I sound excited enough? -D


Thanks to a peptide named NuBCP-9, in fact, this cancer-protecting gene can now be turned into a cancer cell terminator: Researchers at Oregon State University and the Burnham Institute for Medical Research in La Jolla, Calif., have developed a peptide that converts the Bcl-2 protein from a cancer cell’s friend to a foe. This worked both in vitro and in vivo. When injected with this peptide, in fact, mice tumours shrank. The cancer cells simply…died. How about that?


More good news is that, while targeting cancer cells, this peptide has only a minimal effect on normal cells. As we know, this is a big problem with chemotherapy drugs that destroy both the bad and the good cells.


A couple of days ago, after reading my Bcl gene family post, a blog reader/friend sent me a couple of “Blood” studies on Bcl-2, which I still have to read and turn into a post (I am now working on about six or seven different posts…). I admit to finding all of this absolutely enthralling.


Who’d have ever thought that one day I would find studying the complex world of molecules and cells more interesting than teaching English grammar (hehe).


November 30 2008 post. On November 13th (see my “First steps” post) I revealed that I stumbled upon a sort of discovery. Well, it turns out that I hadn’t stumbled at all. I’d already mentioned this supposed “discovery” in previous posts. Sigh, I can’t remember everything I write, I s’pose. ;-) Well, anyway, since my “First Steps” post I have been doing some off and on research (so much to read, so little time…), and today I finally decided to post a few results, even though I still have to sift through a lot of literature. A seemingly endless task…


The “discovery” had to do with the antiapoptotic gene Bcl-x, which is related to Bcl-2 (=B-cell lymphoma 2) and has been linked both to tumour progression and chemoresistance. The overexpression of these two genes protects tumours from chemotherapy in many types of cancer, for instance in squamous cell carcinoma of the head and neck, or SCCHN (see: Oh dear, there are so many studies on this topic but, in a nutshell, the Bcl family is bad news for all of us affected by cancer.


Chemoresistance, by the way, occurs when cancer cells are not affected by chemotherapy. They become immune to the attacks of these drugs. The consequence for chemoresistant myeloma and other cancer patients is obvious…I don’t need to spell it out.


Anyway, my starting point was a rather dated study, titled BCL-X Expression in Multiple Myeloma: Possible Indicator of Chemoresistance and published in 1998 in “Cancer Research” (abstract:; full study: Since it’s available for free online, I won’t go into too many details. But if you just read the Discussion part, you will see that Bcl-x is more likely to be detected in myeloma patients at relapse and correlates with chemoresistance. Bingo.


But let’s get to some potentially good news.


After skimming through that study, I googled the following words: “chemoresistance” and “myeloma.” One of the first links that popped up took me to one of Prof. Aggarwal’s many studies, the one titled Targeting chemoresistance in multiple myeloma cells by curcumin, quoted on the MMRF website.


This didn’t surprise me. I already knew that curcumin inhibits the evildoings of the Bcl family (there are heaps of studies on this). But then I wondered if there could be other natural plant extracts that inhibit it, too? The answer is a resounding YES! And, how odd!, I found all this info on my blog, just by doing a simple search. I hadn’t really made all these connections before now, and this made me think that I really must set up an Excel spreadsheet listing the specific targets of each supplement, in order to make some comparisons. For now, though, this is what I have found:


Bcl-2 inhibitors: nigella sativa (black cumin), gossypol, apogossypol, gambogic acid and omega-3.


Bcl-2 & Bcl-x inhibitors: curcumin, zerumbone, baicalein, resveratrol, ursolic acid, honokiol and capsaicin (=the “hot” stuff in red pepper). There may be others as well, but I stopped looking…for now. By the way, I have Pages on all of these extracts (see the right-hand side of my blog).


This bit of research has opened up a whole new world to me. And it also posed a good question: if I, with no scientific background and with only very meagre means at my disposal (a simple Internet connection), can…stumble upon a possibly useful connection/synergy between the natural and synthetic worlds, a connection that has the real potential to help cancer patients at the very least with the toxic side effects of chemo and possibly even with the treatments themselves (by making the tumour cells more susceptible to these drugs, e.g.), then why the heck don’t MORE cancer researchers devote MORE time to investigating this type of synergy?

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