Parthenolide and myeloma news

June 4, 2008 / / 9 Comments

An aunt and uncle of Stefano’s spent the Xmas 2007 holiday with us. One day I told Stefano’s plant-loving aunt about parthenolide, or PTL, the active myeloma-cell-killing ingredient in the feverfew plant. She recognized the Latin name of feverfew (Tanacetum parthenium) and gasped: “But my mother has this plant growing WILD in her back yard!” Oh, you can imagine my delight at this bit of news! She promised to dig up and send me a bit of this plant as soon as spring arrived. So I now have a pretty little feverfew plant in my front yard (see the photo I took this morning). Now, I am not sure what I will be doing with it (preparing teas, perhaps? The highest concentrations of PTL, I read, are in the flowers and fruit of feverfew) but at the very least I am sure it will bring me good luck.

I used this little story and my photo as an introduction to today’s post about a recent U.S. study on the anti-myeloma effects of partenolide. I have already posted about two previous studies on the same topic–one Chinese, the other Japanese. For background info, please see my Page on parthenolide/DMAPT.

A blogging friend (thank you!!!) sent me the full text of this Indiana University School of Medicine study published in Clinical Cancer Research on March 15th 2008. In the abstract (http://tinyurl.com/5xxsu5) we can read that PTL has multifaceted antitumor effects toward both MM cells and the bone marrow microenvironment. Excellent starting point, I’d say! Okay, with no further ado, I will plunge right into the study.

The beginning of the full study has some interesting wording: Despite intensive chemotherapy, multiple myeloma (MM) remains an incurable, yet chronic, blood cancer with over 14,000 patients diagnosed and 45,000 patients treated yearly in the United States The interaction of MM cells with the bone marrow microenvironment contributes to the heterogeneous treatment response and drug resistance.. Incurable, yet chronic, did you notice that? Hmmm, I think this may be the first study I have looked at so far that mentions the adjective “chronic” in the same breath as “myeloma.” Well, well.

Reading on, when myeloma cells adhere to the bone marrow stromal cells (BMSC), that is, to the cells and the supporting tissue that surround the myeloma cells in our bone marrow, NF-kappaB activation in the BMSCs up-regulates interleukin-6 (IL-6) and vascular endothelial growth factors, which further enhance MM cell growth both directly and, in the case of vascular endothelial growth factor, also indirectly via promoting angiogenesis. Vascular endothelial growth factor is abbreviated as VEGF and, in a nutshell, is a tumour-feeder.

The researchers identify NF-kappaB as the main culprit in the myeloma proliferation process, since it affects both the tumor cells and the supporting microenvironment.

And it just so happens that parthenolide inhibits NF-kappaB (as do curcumin and practically every substance that I have researched and posted about here!). Its anti-tumour effects have been observed in various cancers, including breast, lung, prostate, cholangiocarcinoma, and acute myeloid leukemia. It also increases the effectiveness of chemotherapy, which might be of interest to those who are doing chemo right now.

Interesting titbit: one of the anti-myeloma strategies criticized by the Indiana researchers is the use of Bortezomib (Velcade), in this sense: the proteosomal inhibition in normal cells can lead to significant side effects due to the accumulation of toxins, which would otherwise be removed by a fully functional proteosome. The Indiana researchers argue that targeting NF-kappaB might instead lower toxicities while maintaining efficacy. Hmmm.

At any rate, the researchers tested parthenolide in myeloma cell lines that had become resistant to dexamethasone and doxorubicin. After 72 hours, PTL inhibited the proliferation of these resistant cells.

Now, since I know a few myeloma folks who are taking dexamethasone, here is some info on PTL used with dex. The researchers found out that this combination is synergistic.

Here is the gist: Parthenolide activates both the extrinsic and intrinsic apoptotic pathways, whereas other anti-MM treatments, including conventional chemotherapy, radiation, and glucocorticoid, primarily activate the intrinsic apoptotic pathway. We hypothesize that simultaneous activation of both apoptotic pathways may enhance cytotoxicity. Our finding of an additive cytotoxicity with the parthenolide and dexamethasone combination supports this concept.

Oh, you may ask what “extrinsic” versus “intrinsic” apoptotic pathway means? Good question. Not easy to answer, but basically the death of a cancer cell can be caused by “die, you scoundrel!!!” signals transmitted by so-called “death receptors” located on the cell’s surface, that is, external (to the cell) signals, or by death signals that originate inside the cell such as those deriving from DNA damage or from chemotherapy.

The researchers also found that PTL is toxic only to myeloma cells, not to the surrounding healthy ones. Now, haven’t I read that BEFORE?

Parthenolide also attenuated the protective effect of the bone marrow microenvironment on myeloma cells. And IL-6 was unable to protect the myeloma cells from the toxic effect of this powerful plant extract. For the scientifically-minded: Parthenolide inhibited the NF-kappaB–DNA binding and further reversed the effect of TNF-alpha–induced NF-nB activation.

The study concludes that parthenolide is effective against MM cells in the context of the bone marrow microenvironment and that its mechanisms of action are both caspase-dependent and independent. In combined therapy, parthenolide is additive and synergistic with dexamethasone and TRAIL, respectively. Our findings provide a rationale for the clinical development of parthenolide. (TRAIL, by the way, stands for TNF-related apoptosis-inducing ligand; basically, it helps induce apoptosis in cancer cells.)

How about that?

Italian myeloma fundraising event

June 2, 2008 / / 1 Comment

Today’s post will be of interest mainly to those of us who live in Italy and, in particular, in Tuscany. Through my blog I “met” (we have spoken a few times by phone and plan a get-together as soon as possible) an Italian whose uncle, Mario Schirinzi, a myeloma patient, died in 1996.

Last year, Vittorio, together with a few relatives and friends, set up an association in his uncle’s memory with the main intent of providing information and support to people with myeloma in collaboration with the IMF (International Myeloma Foundation). I would like to highlight that this is the ONLY Italian association that works specifically on myeloma-related issues. Very exciting.

On June 21^st there will be a fundraising event in the form of a golf tournament to be held at the Golf and Country Club Le Pavoniere in Prato (Tuscany). You can read about it in English on the IMF website: http://tinyurl.com/4uluvg: The proceeds from the golf event will go towards a patient meeting seminar to be organized in collaboration with the IMF in Tuscany this fall. Excellent!

For specific information (in Italian), please go to the Schirinzi Association blog, http://mielomahelp.blogspot.com/ If you are a golf player and would like to sign up to play in the tournament, call Le Pavoniere directly or write the Association an e-mail.

After the golf event there will be a roundtable discussion on myeloma. Among the speakers will be Dr. Mario Ladetto, a specialist in blood disorders as well as professor and researcher at the Faculty of Medicine and Surgery of the University of Torino; Gregor Brozeit, the European Director of the IMF, representatives from the Prato branch of the AIL (the Italian association against leukaemias, lymphomas and myeloma) and local authorities from Prato. It should be very interesting!

I strongly urge those of us who live in the area to attend. Stefano, my parents (who are arriving here next week from the States!) and I will be there, and my brother-in-law, a golf player, may actually participate in the tournament. I will be the one asking the speakers about curcumin, other alternative treatments and myeloma stem cells, so I should be easy to identify.

Please come up to me and introduce yourselves! Ci vediamo il 21 giugno! Ciao!

Acid, alkaline or…balderdash?

May 30, 2008 / / 2 Comments

Have you ever come across sentences like these: if your acid-alkaline equilibrium is out of balance, you are making your body prone to disease, low energy, stress and infections? Yes, I have, too. Scary, huh?

The acid-alkaline theory, as it is called, attempts to explain how tumours develop and proliferate. In a nutshell: since cancer cells thrive in an acidic environment, cancer forms when too much acid builds up inside the body. It follows that if we eat alkalizing foods we can prevent or even reverse a cancerous trend. No acid, no cancer. Ah, fantastic. So simple.

Too simple…

The May 2008 newsletter (see: http://tinyurl.com/4ovujo) of the American Institute of Cancer discusses this unsubstantiated theory […] based on lab studies that suggest cancer cells thrive in an acidic (low pH) environment, but cannot survive in alkaline (high pH) surroundings. While these findings are accurate, they apply only to cells in an isolated lab setting. Altering the cell environment of the human body to create a less-acidic, less-cancer-friendly environment is virtually impossible.

Impossible because, generally speaking, our body seeks to maintain a constant equilibrium between acidity and alkalinity. Too much acid in our bloodstream? No problem, it gets excreted via our kidneys. Too much alkali? The kidneys intervene, again. So no matter how many alkaline foods we eat or drink, we cannot change our body’s pH.

Jacob Schor, a naturopathic doctor who works at the Denver Naturopathic Clinic, wrote an interesting report (see: http://tinyurl.com/2oon73) debunking the acid-alkaline theory once and for all. One of his statements, based on recent scientific studies, is that an acidic environment doesn’t cause cancer. Indeed, it’s the other way around: Rapidly growing tumors create an acidic environment lacking in oxygen. […] Changing the pH of a tumor does not change its growth rate significantly, nor does it seem to lead to cell death.

The acid-alkaline theory has some positive features, though, as Jacob points out: it promotes the ingestion of foods that are good for us–fruit and vegetables, e.g.–and tells us to cut down on processed foods that are high in sugar. Good advice.

Ah, by the way, if you have ever thought of buying “alkaline” water, please have a look at Dr. Andrew Weil’s report: http://tinyurl.com/2fplhn. It may save you some money.

I have to confess that, more than a year ago, when I first read about the acid-alkaline theory, I was intrigued enough to print out an acid/alkaline food chart and hang it up in my kitchen. Well, that chart has ended up in the trash can.

Balderdash.

A good reason to avoid sugar

May 28, 2008 / / 16 Comments

The “editor” problem has still not been fixed, but I decided to go ahead and publish a post anyway this morning. You will notice that the tiny urls are not highlighted, so if you want to go and check an abstract, you will have to copy and paste the link. Sorry about that. I hope the problem can be resolved soon! (UPDATE, May 29: the fabulous Healthblogs manager has fixed the formatting/editing problem, so the tiny urls should work now, etc.).

That sugar is bad for folks who have cancer is nothing new. There is a ton of literature on this topic. And the cancer-sugar connection makes sense when you consider that PET scans are able to identify possibly active tumours thanks to radioactive sugar (radioactive sugar…no comment!!!) injected into the body. Since active tumours gobble up sugar much more quickly than healthy cells, the so-called “hot spots” that show up on PET scans could well be cancer cells having a radioactive sugar snack. Scary, when you think of it. (I haven’t had a PET scan yet, but Sherlock had one recently, and it turned out “clean,” by the way, which is super duper! Evviva!).

Anyway, after my diagnosis in 2005, and after reading Quillin’s book, “Beating Cancer with Nutrition,” I cut back on sugar. Way back. For a time I even eliminated it. After a few months, though, I fell off the no-sugar-at-any-costs wagon. I take a bit of honey in my morning cappuccino. I still avoid white and brown sugar as much as possible, but I have resumed eating sweets whenever I feel like it.

Thing is, since reading the study linking stress to myeloma (see my Page on this topic), I have become convinced that it’s worse to crave something sugary and NOT eat it, or eat it and feel guilty!, than just to go ahead and eat it. I don’t fight urges anymore (well, if they are within reason, of course!). My diet is certainly much healthier than it used to be: for instance, I eat heaps of Brassicaceae (broccoli etc.), garlic, onions etc.

But the point of my post today is: why is sugar bad for us? What are the mechanisms involved? Well, researchers at the Duke School of Medicine may have found an answer. According to a recent Science Daily article (http://tinyurl.com/45yrh2), the Duke researchers discovered that sugar is used by tumour cells to avoid programmed cell death (apoptosis): They make use of a protein called Akt, which promotes glucose metabolism, which in turn regulates a family of proteins critical for cell survival […]. So AKT (in its mutant form) apparently keeps cancer cells alive.

The researchers also noticed that when they removed glucose from the environment, Akt was not able to prevent the cancer cells from dying. Aha! One of the researchers commented that Akt’s dependence on glucose to provide an anti-cell-death signal could be a sign of metabolic addiction to glucose in cancer cells, and could give us a new avenue for a metabolic treatment of cancer. Interesting.

Then I read a related Science Daily report (http://tinyurl.com/3or2dj) about glycolysis, a process that turns glucose into energy for cells. Unlike healthy cells that get their energy for growth from both glycolysis and respiration, cancer cells are highly dependent on glycolysis. Highly dependent, huh? More proof that cancer and sugar are good buddies.

The second article tells us that researchers at MD Anderson have now combined two drugs that inhibit glycolysis in human tissue cultures of acute lymphocytic leukemia, thus starving the leukemia cells from their energy source while leaving healthy cells free to get their energy from respiration.

Now I just have to find the time to do some research concerning natural non-toxic ways to inhibit glycolysis without eliminating chocolate chip cookies from my diet…