May 31 2007 post. Without Dr. Benelli’s books (see my Natural COX-2 inhibitors post), I might not have discovered the anti-MM effects of baicalein, one of the main compounds found in Scutellaria baicalensis, also known as Chinese skullcap. In spite of its scary-sounding name, which derives from the peculiar shape of its seed heads, this plant is actually a very friendly member of the mint family (Laminaceae). This online photo shows off its very pretty flowers (in fact, I am thinking of getting one for my back yard): http://tinyurl.com/29cp3f Its yellow root has been (and IS) used in traditional Chinese medicine for the past 2000 years to treat various ailments ranging from irritability (!) to hepatitis. Its healing properties are too many to be listed here, but can be found on many websites. I would just like to mention that it has anti-inflammatory, antioxidant, antitumour, antimicrobial, antifungal, antiviral, free-radical-scavenging properties…okay, enough, enough, this is turning into a laundry list! And more!
Baicalein and MM. Drum roll, please! A 2005 study published in "Blood" is titled: "Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells" (http://tinyurl.com/2jnlej). Suppression of proliferation? Induction of apoptosis in MM cells? Hurray! Scutellaria radix is the dried root of Scutellaria baicalensis (baicalensis, by the way, derives from Lake Baikal, in Siberia, where the plant was first discovered), which is an ingredient in HLJDT, a traditional Chinese medicine. It was found to have anticancer, antiviral, anti-inflammatory and antibacterial properties. Researchers tested its three main components (baicalein, baicalin, and wogonin) separately, and concluded that baicalein had the strongest anti-MM effects. In particular, it inhibited the proliferation of myeloma cell lines and the survival of primary myeloma cells, especially MPC-1- immature myeloma cells, and induced apoptosis in myeloma cell lines via a mitochondria-mediated pathway by reducing mitochondrial membrane potential and activating caspase-9 and caspase-3. Researchers also found that the antiproliferative effect of baicalein is not specific to myeloma cells, since it has also been examined for a human myeloid cell line, HL-60. I have already mentioned these HL-60 cells (see the link to the 2007 University of Pittsburgh study in yesterday’s post). Baicalein also inhibits COX-2, which may occur via the down-regulation of NF-kB. The good news continues: baicalein and Scutellaria radix also have an effect on the infamous IL-6. Yahoo!
Furthermore, baicalein is a potent inhibitor for -glucosidase, which catalyzes the final step in the digestion of carbohydrates. Based on these observations, we cannot exclude the possibility that the baicalein-induced inhibition of myeloma cell proliferation and induction of apoptosis result from not only the down-regulation of NF-kB activity but also various other actions of baicalein. So baicalein will kill my MM cells using different mechanisms AND reduce the impact of my dinner pasta carbs on my blood sugar at the same time. Now, that’s what I call a find! The study concludes: The results presented here clearly show that baicalein (or Scutellaria radix) can directly inhibit the proliferation of myeloma cells and present enough evidence for clinical trials to treat multiple myeloma. Indeed! Unfortunately, I was unable to find any clinical trials listed for Scutellaria, except for a Phase I/II trial (http://tinyurl.com/2oyohu) that is testing Scutellaria barbata D. Don, or barbed skullcap (a relative of our Scutellaria baicalensis), for advanced metastatic breast cancer. See this BBC News report: http://tinyurl.com/2vbf9u I mention this report mainly because I loved (and borrowed, thank you!) the headline: Mint leaf starves cancer to death !
Other studies. A 2003 study (http://tinyurl.com/2zt9bt) examines the effect of baicalein on the central nervous system, concluding that it has neuroprotective effects. And Scutellaria baicalensis was tested in head and neck squamous cell carcinoma (HNSCC), which is resistant to chemotherapy, in vitro and in vivo (http://tinyurl.com/262awe). The study concludes that Scutellaria baicalensis appears to have many anti-cancer mechanisms. If you are squeamish, do not click on this link, which posts the photo of a mouse with huge tumours. I was horrified. I know, I know. Also, here is a prostate cancer and baicalein study: http://tinyurl.com/yvggld I will stop here.
Concluding remarks on Scutellaria and MM. An April 2007 study (http://tinyurl.com/3xcwjw) confirms that Scutellaria baicalensis and baicalein (in particular) have anti-proliferative and apoptotic activity against acute lymphocytic leukemia, lymphoma and myeloma cell lines. Another recently published study (http://tinyurl.com/2useyn) shows that baicalein combined with Dexamethasone suppress the growth of MM cells. Researchers report that this combination also reduced the expression of IL-6, as we have seen. The study states that the cooperative growth suppression of Dex and baicalein in myeloma cells might be useful for myeloma therapy. Combinatory treatment with both may overcome the Dex resistance and the baicalein resistance in primary myeloma cells, as well as myeloma cell lines. Good news for those MMers undergoing chemotherapy.
Where are those baicalein-MM clinical trials???
UPDATE. December 2nd 2007 post: I am doing the groundwork for my Scutellaria baicalensis experiment, which has brought me to view a few new studies, such as one published in the November 2007 issue of Molecular Cancer Therapeutics, see abstract: http://tinyurl.com/266g6y (many thanks to a new friend for sending me the full study AND also to my friend Sherlock for trying to locate it).
Here’s a quick review taken from this study (you can also see my Page on Scutellaria baicalensis). Baicalein, extracted from the root of Scutellaria baicalensis, is an active flavonoid that has been found to have anticancer properties, leading to cell cycle arrest and suppression of proliferation in cancer cells. And yes, in case you were wondering, that includes myeloma cells in vitro only, thus far. Hence, my upcoming experiment on myself.
Baicalein (just like curcumin, let me add: see my link to the article on curcumin and survivin, right-hand side of my homepage) reduces the expression of survivin, a protein that inhibits apoptosis in cancer cells, including myeloma cells. If you need convincing that survivin (not to be confused with the adjective SURVIVING, by the way!) has relevance for myeloma, take a look at this February 2007 "Leukemia" abstract: http://tinyurl.com/2s9xon My comment: survivin may be fascinating, but, according to the above-mentioned Molecular Cancer Therapeutics study, it is associated with decreased survival, unfavorable prognosis, and accelerated rates of recurrences in cancer therapy. Nothing fascinating about that, methinks
Anyway, the Molecular Cancer Therapeutics study suggests that the inhibition of CDC2/cyclin B1 by baicalein contributes to the reduction of survivin and the proliferation inhibition in cancer cells. CDC2 is a kinase also present in myeloma hmmm. Six flavonoids, baicalin, catechin, genistein, quercetin and rutin, in addition to baicalein, were examined by these researchers. The most toxic to bladder cancer cells was found to be baicalein, which was, and, this is significant!, NOT toxic to healthy cells. Does that sound familiar?
I have read the same thing over and over again: Toxic to cancer cells, Not Toxic to healthy cells! Okay, so where ARE the clinical trials!?! Well, quelle coincidence (!), since I wrote my May 31st post on Scutellaria baicalensis, two more clinical trials testing Scutellaria-derived substances have been added to the one I mentioned. One is testing an aqueous extract from herba Scutellaria Barbata D. Don on metastatic breast cancer patients; the other is testing a botanic formulation called PHY906, consisting of: Scutellariae baicalensis Georgi, white peony root, licorice, and the fruit of Fructus ziziphi (date). According to the patent application (see: http://tinyurl.com/28sfez), This specific formulation was established more than 1500 years ago for the treatment of diarrhea, abdominal spasms, fever, headache, vomiting, nausea, extreme thirst, and subcardial distention, and each herb possesses a distinct pharmacological profile that includes anticancer and antiviral activity, hematological and immunological stimulation, analgesic activity, vasodilation, liver protection, antioxidation, and appetite improvement. PHY906 is being tested together with a chemo drug on advanced pancreatic cancer patients. Well, three trials are better than just one, I suppose. If you want to read more about these trials, just go to http://tinyurl.com/28gasl
Speaking of clinical trials, according to the Molecular Cancer Therapeutics study, "Although this study provides the potential cancer therapy of baicalein by human cancerous cells in vitro, the human cancer therapeutics by baicalein or combination of the survivin gene knockdown need to be determined by in vivo model before clinical trials. Moreover, the possible pharmacokinetic and toxicologic barriers need further characterization." Very true, but let me point out that Scutellaria baicalensis has been used as an anti-inflammatory remedy in traditional Chinese medicine for more than 2000 years to treat fevers, hypertension, coughing, and other ailments, according to "Drugs dot com" (see: http://tinyurl.com/2d5fvj). This brings me to my warnings section.
Warnings: according to the Memorial Sloan-Kettering website, Scutellaria baicalensis MAY cause stupor, confusion, and seizures. Am I worried about that? Naaaah, not in the slightest. In the past, I have taken HUGE doses of antibiotics, even recently (now that I think about it), and if you paid any attention to the list of possible side effects associated with half the stuff you take for common ailments, you wouldn’t let it come within a few meters of you, let alone swallow it (or, worse, have your mother-in-law inject it into your hip, as happened to me earlier this fall when I was forced to take elephant-doses of antibiotics for a case of acute bronchitis ). The only other big warning about Scutellaria is that it may interact with cyclosporine, a drug that suppresses the immune system. And then there are the usual pregnancy or breastfeeding warnings, which don’t apply to my case anyway.
UPDATE. December 3rd 2007 post: I got my hands on a very interesting study that I looked at more carefully this morning. Published in the November 2007 issue of Clinical and Molecular Allergy, the study is titled: Baicalein inhibits IL-1b- and TNF-a-induced inflammatory cytokine production from human mast cells via regulation of the NF-kB pathway. Let’s quickly examine the title. IL-1beta is an inflammatory cytokine that is a potent inducer of the important myeloma growth factor, IL-6. (see these two Mayo Clinic study abstracts from 2006 and 2007, respectively: http://tinyurl.com/2hu4am and http://tinyurl.com/27ffa4). Anything that induces IL-6 is no friend of mine! I am almost certain that I have already written about TNF-alpha, or tumour necrosis factor-alpha, but just in case I haven’t, here goes: it is a growth and SURVIVAL factor for myeloma cells, albeit not as powerful as IL-6. So, also not good news for us.
A few remarks on human mast cells. As the abstract (see: http://tinyurl.com/24f2ge) informs us, these are multifunctional cells capable of a wide variety of inflammatory responses. According to the full study, these cells accumulate wherever there is an inflammatory process going on and even mediate the production of inflammatory cytokines. Now, that’s really no good, no good at all, especially since "Inflammatory cytokines are important factors in chronic inflammation, allergy, asthma, atherogenesis, and autoimmune diseases." Reading on, we are told that mast cells have been implicated in acute and chronic inflammatory responses and in many diseases characterized by inflammation. Oh, and read this: activated mast cells secrete IL-6! Tsk, tsk. Bad BAD mast cells!
Another interesting bit: The activation of NF-kB requires phosphorylation and proteolytic degradation of the inhibitory protein IkBa. This sentence takes us back to the discussion section of the 2005 Blood study on baicalein and myeloma (full text: http://tinyurl.com/2jnlej). I quote: NF-kB regulates the expression of many genes (IkB-a, Bcl-xL, IL-6, and cyclin D1) important for the proliferation and survival of myeloma cells.
Well, on page 16, the November 2007 study states: "The results suggest BAI inhibits the NF-kB activation via inhibition of IkBa phosphorylation and degradation." BAI, by the way, stands for baicalein.