June 20 2009 post. While working on my, er, upcoming STAT3 post (=in draft mode for months now!), I came across an anti-myeloma substance called butein (see: http://tinyurl.com/lu4jny). It is an active extract of Rhus verniciflua Stokes (and of other plants as well, such as the stem-bark of cashew trees), a medicinal plant that has been used for ages in Asian countries to treat pain, thrombosis, gastritis, stomach cancer and parasitic infections. I also read that it is used as a food additive in Korea, which would seem to guarantee its non-toxicity…


In recent years, butein has been found to have anti-proliferative effects on a number of cancer cells, including breast cancer, colon cancer, osteosarcoma, lymphoma, acute myelogenous leukemia, melanoma and hepatic satellite cells. I also found a study on bladder cancer cells showing that butein inhibits the activation of NF-kappaB as well as halting metastasis. (I can provide links to all these studies upon request.)


A 2007 MD Anderson study (see: http://tinyurl.com/n5yx9k; click on “manual download” if the automatic one doesn’t work) proves that Butein inhibited the constitutive NF-kB activation in MM cells. These results indicate that butein can suppress not only inducible but also constitutively active NF-kB in tumor cells. (The more I read, the more I like this stuff…)


The myeloma-butein study (grazie, Sherlock!) that I mentioned at the beginning of this post was published in “Molecular Pharmacology” in 2009. MD Anderson researchers found that butein inhibited both constitutive and interleukin-6-inducible STAT3 activation in multiple myeloma (MM) cells. Without (yet) going into details about the STAT3 signaling pathway, let me just mention that its inhibition is good news for us.


More titbits: butein also inhibits the wicked members of the Bcl family, cyclin D1 and Mcl-1…all of this led to the suppression of proliferation and induction of apoptosis. And also: butein significantly potentiated the apoptotic effects of thalidomide and Velcade in MM cells. In fact, according to these researchers, butein may have the power to reverse chemoresistance in myeloma cells.


Because of time constraints, I must jump directly to the results and discussion parts. Note: the researchers tested butein also on prostate cancer and head and neck cancer cells. They found that butein inhibits the activation of STAT3 in these cancer cells as well…both constitutive and inducible STAT3 activation (by the way, the inducible type, which can be caused by icky nasty IL-6, was suppressed 100% by butein in lab tests!).


Then we have a long list of butein’s anti-myeloma properties. Impressive, but I decided against posting all these various activities, since that would make my post look like an incredibly lengthy laundry list. Here, though, is an important excerpt: butein significantly enhanced the apoptotic effects of Velcade from 20 to 70% and of thalidomide from 5 to 55%. Well, well…


At the end of the study, the researchers argue that the pharmacological safety of butein and its ability to down-regulate the expression of several genes involved in cell survival and chemoresistance and potentiate the effect of Velcade and thalidomide provide a sufficient rationale to further carry out preclinical studies preceding human trials.


Hear hear!

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