Posted on 03/03/2011 11:39:59 AM PST by decimon
Discovery of molecular mechanism reveals antitumor possibilities
Researchers at the Johns Hopkins School of Medicine have discovered that a natural product isolated from a traditional Chinese medicinal plant commonly known as thunder god vine, or lei gong teng, and used for hundreds of years to treat many conditions including rheumatoid arthritis works by blocking gene control machinery in the cell. The report, published as a cover story of the March issue of Nature Chemical Biology, suggests that the natural product could be a starting point for developing new anticancer drugs.
"Extracts of this medicinal plant have been used to treat a whole host of conditions and have been highly lauded for anti-inflammatory, immunosuppressive, contraceptive and antitumor activities," says Jun O. Liu, Ph.D., a professor of pharmacology and molecular sciences at Johns Hopkins. "We've known about the active compound, triptolide, and that it stops cell growth, since 1972, but only now have we figured out what it does."
Triptolide, the active ingredient purified from the plant Tripterygium wilfordii Hook F, has been shown in animal models to be effective against cancer, arthritis and skin graft rejection. In fact, says Liu, triptolide has been shown to block the growth of all 60 U.S. National Cancer Institute cell lines at very low doses, and even causes some of those cell lines to die. Other experiments have suggested that triptolide interferes with proteins known to activate genes, which gives Liu and colleagues an entry point into their research.
The team systematically tested triptolide's effect on different proteins involved with gene control by looking at how much new DNA, RNA and protein is made in cells. They treated HeLa cells with triptolide for one hour, compared treated to untreated cells and found that triptolide took much longer to have an effect on the levels of newly made proteins and DNA, yet almost immediately blocked manufacture of new RNA. The researchers then looked more closely at the three groups of enzymes that make RNA and found that low doses of triptolide blocked only one, RNAPII.
But the RNAPII enzyme complex actually requires the assistance of several smaller clusters of proteins, according to Liu, which required more investigative narrowing down. Using a small gene fragment in a test tube, the researchers mixed in RNAPII components and in some tubes included triptolide and some not to see which combinations resulted in manufacture of new RNA. Every combination of proteins that included a cluster called TFIIH stopped working in the presence of triptolide.
But again, TFIIH is made of 10 individual proteins, many of which, according to Liu, have distinct and testable activities. Using information already known about these proteins and testing the rest to see if triptolide would alter their behaviors, the research team finally found that triptolide directly binds to and blocks the enzymatic activity of one of the 10, the XPB protein.
"We were fairly certain it was XPB because other researchers had found triptolide to bind to an unknown protein of the same size, but they weren't able to identify it," says Liu. "
To convince themselves that the interaction between triplotide and XPB is what stops cells from growing, the researchers made 12 chemicals related to triplotide with a wide range of activity and treated HeLa cells with each of the 12 chemicals at several different doses. By both counting cells and testing XPB activity levels, the team found that the two correlate; chemicals that were better at decreasing XPB activity were also better at stopping cell growth and vice versa.
"Triptolide's general ability to stop RNAPII activity explains its anti-inflammatory and anticancer effects," says Liu. "And its behavior has important additional implications for circumventing the resistance that some cancer cells develop to certain anticancer drugs. We're eager to study it further to see what it can do for future cancer therapy."
###
This research was supported in part by discretionary funds from the Johns Hopkins Department of Pharmacology and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
Authors on the paper include Denis Titov, Qing-Li He, Shridhar Bhat, Woon-Kai Low, Yongjun Dang, Michael Smeaton and Jun O. Liu of Johns Hopkins; Benjamin Gilman, Jennifer Kugel and James Goodrich of the University of Colorado, Boulder; and Arnold Demain of Drew University, Madison, N.J.
Ping
if this is a ping list for this type of subject, would you consider putting me on it, please? ^_^
thunder god vine? cool.
Gotta wonder how a vine gets so named.
“We’ve known about the active compound, triptolide, and that it stops cell growth, since 1972,”
BUT
only now have we figured out what it does.”
IT ONLY TOOK 39 YEARS.
So if the active ingredient in this stuff is known to kill the reproduction of all sixty National Cancer Institute cell lines, what would discourage a cancer patient from taking some of the thunder god vine? Couldn’t hurt, could it?
Here's some info on it: http://wiki.medpedia.com/Thunder_God_Vine
I never bought into Eastern medicine. the way it was lauded seemed to make it out as the second coming, but without any proof. Just a "It works!" from pale, emasculated liberals who saw any alternative to Western ways as a good thing, because they were in a constant state of rebellion against their parents' values, even as adults. I grew up around proponents of it who were mostly ignorant hippies, and well, hippies smell.
Flash forard 20 years: My back is killing me. I have worn out and crushed my discs due to 25 years of high-impact mountain biking; I'm at the point where I may never get on a bike ever again, and i can't even roll over in my bed without it hurting a lot. I can't be always popping pills because they make me a zombie, and my near-constant pot smoking is bad too, although it is not nearly as zombie-inducing as the pills.
My docs are tired of me; they have no cure, and they shuttle me off to other docs, the last of which simply wants to inject cortizone into my spine every 6 months (not an acceptable long-term solution).
My wife forced me to go to an acupuncturist. Eureka! My pain, while not 100% abated, is almost gone, and I can roll over at night without waking up and resorting to gymnastics. I am now a believer.
In this one area, I side with the stinky hippies.
The type of research as in this article is what I’ve been waiting for with regard to ‘folk medicine.’ Put it to the test to see what works.
Glad you’re getting some relief for your back injury.
Thank you—very helpful.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.