Olive leaf extract kills myeloma cells!

Here we go again. First it was mint leaves, now it’s olive leaves. Yesterday I was looking up something entirely different when I came across oleanolic acid, which is a triterpenoid (how’s that for a mouthful?) compound extracted from plant sources and food (even seedless raisins, I read). But it is also extracted from olive leaves (olea = olive). Olive leaves? Yes, I read that correctly: the leaves of Olea europaea, the common olive tree. I couldn’t stop reading, since I live in a country, indeed a region, famous for its delicious extra virgin olive oil (rightly so). Plus, my cousin is an extra virgin olive oil taster (yes, just like a sommelier, except she tastes and judges olive oil), and our wonderful extra virgin olive oil is given to us by a friend who owns an olive grove here in Tuscany.

So, just for the heck of it, I googled oleanolic acid and myeloma and, wouldn’t you know it?, there it was: a study on an olive leaf extract and MM cells, co-authored by Dr. Kenneth Anderson and published in "Molecular Cancer Therapeutics" in 2004. The full study can be read at: http://tinyurl.com/2okvod It is quite technical, but the conclusion is clear: a synthetic version of oleanolic acid, known as CDDO-Im, induced apoptosis in myeloma cells.

I called my husband, who laughed boy, those MM cells get killed by practically anything, don’t they? (Don’t we wish?!!!) But it (almost) seems to be true: any plant extract that I have looked up so far, and that has been tested in vitro against MM cells, appears to have an apoptotic effect on these malignant cells. Hmmm. Anyway, back to us and the oleanolic acid-MM study. In the Introduction, we can read that Chemoresistant MM cells have also been reported to inactivate anticancer drugs more efficiently than chemosensitive MM cells […]. In this regard, increases in the expression of glutathione (GSH) or the activity of GSH-related enzymes in MM cells has been associated with resistance to anticancer drugs […]. Novel treatment approaches that overcome such chemorefractory mechanisms may therefore be effective in the treatment of MM. CCDO-Im reduces the levels of GSH, which leads to the apoptosis of MM cells. The study continues: we analyzed the effects of the CDDO C-28 imidazolide ester (CDDO-Im) on MM cells. CDDO-Im is a potent inducer of apoptosis in MM cell lines and primary MM cells. Potent inducer of apoptosis in MM cells? What??? Hold on a sec, I’ll be right back. I am just going to pop over to ask my neighbour for some olive leaves from his gorgeous olive tree (see photo)! I could juice them! (Just kidding or am I? πŸ˜‰ ) detail of my neighbour's olive tree

Other effects of oleanolic acid. It has anti-inflammatory, hepatoprotective and anti-hyperlipidemic properties, see this 1995 study: http://tinyurl.com/2aa7vm It has anti-HIV activity, according to this 1999 study: http://tinyurl.com/ypahk9, and wound-healing potential (http://tinyurl.com/ytczrr). A 1999 study (http://tinyurl.com/2rhdpu) tells us that it suppresses the abilities of various inflammatory cytokines, such as IFN-, interleukin-1, and tumor necrosis factor-, to induce de novo formation of the enzymes inducible nitric oxide synthase (iNos) and inducible cyclooxygenase (COX-2) in mouse peritoneal macrophages, rat brain microglia, and human colon fibroblasts. CDDO will also protect rat brain hippocampal neurons from cell death induced by beta-amyloid. A 2003 study suggests that it be used in breast cancer therapy: http://tinyurl.com/338z7b. It also "can provide a cheap and accessible source of additive to conventional treatment of hypertension, complicated by stenocardia and cardiac failure" (http://tinyurl.com/yo2pvv). There seems to be no end to its potential. Oh, it also fights the bacteria that cause cavities and gum disease, so make sure you include oleanolic acid-containing raisins in your diet. Oleanolic acid can also be found in medicinal herbs such as ligustrum, forsythia, and swertia, which are used in China to treat hepatitis. I will stop here, but there would be much more.

Last but not least, according to the IMF website (http://tinyurl.com/3dlsmr), Johns-Hopkins and Dartmouth are testing oleanolic acid, which is now in the preclinical stage. In fact, this excellent bit of news is hot off the press, see the May 22 issue of the Myeloma Minute: http://tinyurl.com/22faba!

Curcumin Brands and Other Issues

I have not posted about brands. As I have previously written, I do not want to make it seem as though I favour one brand over another. The fact is that I don’t know if there exists a best brand of curcumin. So why am I writing this post today? Simple. To help others in a situation similar to mine. If someone had given me any information about curcumin when I started taking it, I would have wasted less time looking up brand information, bioavailability issues, side effects, etc. These were the main reasons for creating this blog. Plus, I have privately received valuable information from other curcumin-takers, some of whom have been taking curcumin for longer than I have. That information should not go to waste.

So how do you choose what brand to take, and how do you decide if one curcumin-offering website is more reliable than another? These are legitimate questions. Please check my Curcumin Protocol post and page, and if you don’t find an answer there, remember that I will readily exchange information privately on this and other matters. Just write to me (if you know my e-mail) or leave me a note here, and I will get in touch with you. I may not be able to answer your questions, but I will try, at least! I should note that I am bilingual (Italian and English), plus I know enough French and Spanish to get by, so you can write to me in these four languages. Latin, too, if you wish. πŸ˜‰

A slightly annoying note. Italian customs in Milan stopped a package containing resveratrol that my parents sent to me in May. They are just doing their job, but this means that I have now run out of the good resveratrol, and am taking what probably is not good enough for my resveratrol experiment. So, I fear that I will have to redo the experiment next fall. The latest word on the package is that customs has lost it. Sigh.

In spite of the customs mix-up and the horrible summer heat wave that is about to hit Florence (sigh), I have a few positive news items. My new kitten is adorable; I visit it every day. It is more interactive now, and looks up at me in wonder, as though it already knows how much I love it. Yesterday the little critter tried to show me how well it can clean itself but kept falling over in vain and clumsy attempts to clean its tiny hind paws. Too funny! Why it ? Well, we still can’t figure out if it’s a boy or a girl! I think it’s a girl, but could well be wrong. And the lonely kitten (see recent blog photo) has been adopted by a very pleasant young woman who passed a strict oral examination yesterday. πŸ˜‰ And, last but not least, a close listserv friend, who had received what seemed to be very worrisome news about her MM, received some good news from a well-known MM specialist (hurray!). Life is good.

Withanolides and MM

A blog friend recently sent me a list of substances that he found while doing research on another health-related topic. I am deeply obliged to him (thank you!) for telling me about another funny-sounding but deadly-to-cancer-cells compound: withanolide. Surprise surprise, in 2006 an MD Anderson team made the discovery that withanolides kill MM cells in vitro. The full study, published in Molecular Cancer Therapeutics, is available online: http://tinyurl.com/2eq3pc The study abstract begins: The plant Withania somnifera Dunal (Ashwagandha), also known as Indian ginseng, is widely used in the Ayurvedic system of medicine to treat tumors, inflammation, arthritis, asthma, and hypertension. Chemical investigation of the roots and leaves of this plant has yielded bioactive withanolides. Earlier studies showed that withanolides inhibit cyclooxygenase enzymes, lipid peroxidation, and proliferation of tumor cells. But even more importantly (for us MMers), in addition to suppressing the nasty COX-2 enzyme, these compounds blocked the activation of NF-kB in human myeloma (U266) cells. Yippee! And I would like to mention that a 2004 study shows that an extract of Withania somnifera inhibited angiogenesis: http://tinyurl.com/ypq58h

A 2003 University of Michigan study (http://tinyurl.com/yqmgxh) tells us that the roots of Withania somnifera are used as a dietary supplement around the world. Furthermore, from what I have read online, Withania somnifera is non-toxic, non-addictive and has no negative side effects (but I should say that I am still looking into this matter). Indeed, a recent study demonstrated that a purified standardized extract of ashwagandha protected the heart from the well-known cardiotoxic effects of doxorubicin: http://tinyurl.com/3yjcno And withanolides may also be effective against arthritis, see this June 2007 study: http://tinyurl.com/2vfw7r

The above-mentioned 2006 MD Anderson study concludes: Overall, our results suggest that the antiproliferative, proapoptotic, anti-invasive, antiosteoclastogenic, antiangiogenic, antimetastatic, radiosensitizing, antiarthritic, and cardioprotective effects assigned to withanolide may be mediated in part through the suppression of NF-kB and NF-kB-regulated gene products. Did I read anti-osteoclastogenic? Ahhhh, that rings a bell. This is a fascinating study, and not difficult to read, so I would urge all MMers to have a look at it.

Right now I am living in my fantasy world where MMers are killing off their nasty MM cells by taking a mixture of all these non toxic compounds. No horrible side effects, no pain. Some day, some day. Okay, out of my fantasy world and off to visit my kitten next-door now. Expect some photos over the weekend! πŸ˜‰

Lonely Kitten and Cleaning Teeth with Turmeric

I have been busy today and haven’t been able to do any research. So I am posting another kitten photo, taken this morning in my neighbours’ yard. πŸ˜‰ Two of the kittens were adopted yesterday by a loving couple, so I am relieved. lonely kittenThe third sibling was left behind, though, and appears to be very sad, even though it is still with its mother. Doesn’t this photo just tug at your heart strings? Poor little dear.

The most recent name suggestions from my family and listserv/blog friends for our three-week-old kitten are: Pammy, Petunia, Paloma, Pillola (which means “pill” in Italian) for a female; Pedro, Picasso, Paco, Philo, Pascal, Pasquale, Palmiro for a male. The name contest is still open!

This morning I read an interesting article titled “Forget fluoride – try turmeric.” In an attempt to stop the water supply in Onehunga, an Auckland suburb, from being flooded with fluoride, a New Zealand biochemist is trying to promote the idea that it is much safer to brush our teeth with turmeric. Since curcumin, turmeric’s active ingredient, has well-known antibacterial and anti-inflammatory properties, he is undoubtedly right! See: http://tinyurl.com/28cf85 Hmmm, but wouldn’t our teeth be stained yellow? I may do a test, just to see what happens…

Gossypin: Not Just Idle Talk!

No, this is not one of my humour posts. This is quite serious. πŸ™‚

Gossypin is an antioxidant, anti-inflammatory flavone extracted from Hibiscus vitifolius, also known as tropical rose mallow, a perennial shrub. In 1978, this flavone (see: http://tinyurl.com/2gdp5l) was found to be effective against arthritis. It was compared to the standard nonsteroid anti-inflammatory agent phenylbutazone against various experimental models of inflammation and increased vascular permeability. The researchers found that gossypin was not as strong as phenylbutazone, but also not as toxic. And, while I am on the subject of pain relief, a 1997 study (http://tinyurl.com/2t37nz) concluded that gossypin could be used as a substitute for morphine, as it is well tolerated and is not habit-forming. Gossypin also has neuroprotective properties, see this 2004 study on rat cortical cells: http://tinyurl.com/yvwmws

But I saved the best news (for us MMers) for last. A 2003 study (http://tinyurl.com/ytdkxj) demonstrated gossypin’s antioxidant, antitumour and anti-carcinogenic properties. Gossypin reduced the tumour size in what were called solid tumor harboring animals, increasing their life span. And, even more significantly, the June 2007 issue of Blood features a study (http://tinyurl.com/2x4p5e) by an MD Anderson team, including Prof. Bharat Aggarwal, showing that gossypin inhibits the infamous NF-kB, suppresses the proliferation of COX-2, and enhances apoptosis of tumour cells. The abstract concludes that gossypin inhibits the NF-kB activation pathway, which may explain its role in the suppression of inflammation, carcinogenesis, and angiogenesis. Gossypin also blocks osteoclastogenesis. Excellent news.

Another non-toxic substance gets added to my to-be-watched-carefully list. πŸ˜‰

Don’t Boil Your Brassicas

This started out as an anti-microwave post. I have never cooked anything in our combination microwave oven and grill, and don’t like to use it even for defrosting (but I do, on occasion). So this morning when I began reading a recent study on loss of nutrients in Brassica vegetables (cabbage family), I was absolutely convinced that microwaving would turn out be the worst cooking method. I already had a catchy title for my post: Don’t Nuke Your Brassicas. Well, I stand corrected (or do I?).

According to a University of Warwick study (http://tinyurl.com/3dmcfh), published in the February 2007 issue of Food and Chemical Toxicology, the worst way to cook Brassica vegetables is to boil them. The study data shows that the boiling of Brassica vegetables for 5 minutes leads to losses of 20 – 30% and for 10 minutes losses of 40 – 50%. And, in fact, 90% of the precious glucosinates ended up in the cooking water. According to the news release on the study (http://tinyurl.com/2h4f57), steaming for up to 20 minutes yielded no significant loss of glucosinate content, nor did stir-frying for five minutes or cooking in the microwave for up to three minutes. Surprise!

Okay, but what about microwave cooking? I then read the abstract of a 2003 study (http://tinyurl.com/adko8) reporting that the worst cooking method for broccoli is microwaving, which involves a flavonoid loss of 97%. Okay, this is what I expected. I should note that a significant nutrient loss was seen also with boiling.

Final consideration: Although the results of these two studies differ in part (boiling versus microwaving), they both confirm that the best way to cook vegetables is to steam them. Well, that is nothing new, right?

A note on glucosinolates. Trust me to find funny-sounding names! Before reading the University of Warwick study, I had never heard of these compounds. According to Wikipedia, glucosinolates are a class of organic compounds that contain sulfur, nitrogen and a group derived from glucose, typical of the Brassicaceae. The cancer-preventive potential of glucosinolates are discussed in the above-mentioned University of Warwich news release and in another 2007 British study (http://tinyurl.com/2mb3jp). The latter study, by the way, confirms the findings of previous ones that raw Brassica vegetables have a higher glucosolinate content than cooked vegetables. Now, that makes sense!

New Kitten

Pronto or Paloma?Yesterday afternoon we went to visit our new kitten at our neighbours’ house. My husband picked it (still don’t know its gender) up, see photo. So far, I have received the following name suggestions from MM listserv friends:

If it’s a male: Pronto, Pablo or Pascale. If it’s a female: Paloma, Phaedra, Petra or Pernilla. The name contest is still open!

I’m off to watch a movie. Have a great Sunday!

Curcumin Research Award

A first-year medical student at the LSU Health Sciences Center at the Shreveport School of Medicine won the American Society of Hematology (ASH) Trainee Research Award for “excellence in cancer research.” His project at LSUHSC-S “will focus on chemoprevention of head and neck cancers with curcumin.” I found this titbit in the June 8 issue of the Shreveport Times: http://tinyurl.com/2a7nfp

Could the tide finally be turning?

Friday Humour: Do Cats Go to Heaven?

From a close MM listserv friend (thanks!!!):

A cat dies and goes to Heaven. God meets him at the gate and says, “You have been a good cat all of these years. Anything you desire is yours, all you have to do is ask.”The cats says, “Well, I lived all my life with a poor family on a farm and had to sleep on hardwood floors.”

God says, “Say no more.” And instantly, a fluffy pillow appears.

A few days later, 6 mice are killed in a tragic accident and they go to Heaven. God meets them at the gate with the same offer that He made the cat. The mice said, “All our lives we’ve had to run. Cats, dogs and even women with brooms have chased us. If we could only have a pair of roller skates, we wouldn’t have to run anymore.”

God says, “Say no more.” And instantly, each mouse is fitted with a beautiful pair of tiny roller skates.

About a week later, God decides to check and see how the cat is doing. The cat is sound asleep on his new pillow. God gently wakes him and asks, “How are you doing? Are you happy here?”

The cat yawns and stretches and says, “Oh, I’ve never been happier in my life. And those Meals on Wheels you’ve been sending over are the best!”

Tree Sap Zaps MM Cells

I borrowed the first part of this post title from a CBS report (http://tinyurl.com/2crn7b) on the cholesterol-lowering effect of guggulsterone, extracted from the guggul tree’s gum resin. But cholesterol-lowering is perhaps the least important property of guggulsterone.

An MD Anderson research team has just published a study on this remarkable sap extract, see the June 2007 issue of Biochemical Pharmacology (the abstract can be read at: http://tinyurl.com/38jlon). Thanks to a close MM Italian friend (grazie, e ci vediamo domani, speriamo non piova!), I was able to read the full study. Guggulsterone is a plant polyphenol obtained from the gum resin of the Commiphora mukul tree (more familiarly known as the guggul tree, don’t you love that name? My original post title was “Google Guggul”! πŸ˜‰ ). As with many other substances on my research list, this is not a new discovery. Guggulsterone has been used by Chinese and Ayurveda (ancient Indian healthcare system) medicine for centuries to treat a variety of disorders, including obesity, diabetes, hyperlipidemia, atherosclerosis, and osteoarthritis

As always, my favourite part of a scientific study is the conclusion: Guggulsterone inhibited the proliferation of human leukemia, head and neck carcinoma, multiple myeloma, lung carcinoma, melanoma, breast carcinoma, and ovarian cancer cell lines in a dose-dependent manner. It also blocked the proliferation of dexamethasone-resistant MM1 cells and doxorubicin-resistant breast cancer cells, and inhibited the villainous COX-2. I could dance with joy! But there is more good news.

The study also indicates that, because of lack of any known toxicity, guggulsterone should be further explored for its anticancer potential. Whether the concentrations used in our studies can be achieved in vivo, is unclear at present. [ ] Overall, our results indicate that guggulsterone inhibits the growth of wide variety of cells and induces apoptosis through downregulation of antiapoptotic gene products, modulation of cell cycle proteins, activation of caspases, inhibition of Akt and activation of JNK. As usual, the big problems are bioavailability and dosage, and, of course, testing in clinical trials.

A 2004 study (MD Anderson, again!) shows that guggulsterone suppresses NF-kB and NF-kB-regulated gene products, which may explain its anti-inflammatory activities. See: http://tinyurl.com/2w4buj And remember my post on curcumin, osteoclasts and bone resorption? Well, a 2006 study (http://tinyurl.com/2oa8zk) by the fabulous MD Anderson researchers confirms that guggulsterone is another substance that suppresses RANKL and tumor cell Γ’β€šΒ¬”induced osteoclastogenesis by suppressing the activation of NF-kB. Ayurvedic medicine, by the way, has used guggulsterone for centuries to treat bone fractures and ostheoarthritis. So it comes as no surprise that this particular study shows that guggulsterone suppressed osteoclastogenesis induced by MM. More dancing!

So, let’s see: here we have a non toxic substance that has been used in traditional medicine for hundreds, perhaps thousands, of years and that has been shown to work against MM, osteoclastogenesis, COX-2, NF-kB, etc. Well, it certainly doesn’t take a genius to figure out that more research needs to be conducted on this and many other non toxic substances.

Let’s get the research ball rolling!