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UPMC — A natural anthocyanidin found in many fruits and vegetables (as well as red wine) selectively kills leukemia cells in culture while showing no discernible toxicity against healthy cells, according to a study by researchers at the University of Pittsburgh School of Medicine. These findings, published online March 20, 2007 in the Journal of Biological Chemistry, offer hope for a more selective, less toxic therapy for leukemia, and perhaps for a flavonoid-optimized nutritional strategy for preventing cancers.
“Current treatments for leukemia, such as chemotherapy and radiation, often damage healthy cells and tissues and can produce unwanted side effects for many years afterward. So, there is an intensive search for more targeted therapies for leukemia worldwide,” said corresponding author Xiao-Ming Yin, M.D., Ph.D., associate professor of pathology, University of Pittsburgh School of Medicine.
Based on previous reports that anthocyanidins - a group of natural flavonoids found in cherries, currants, blueberries, cranberries, red cabbage, and eggplant - have chemopreventive properties, Dr. Yin and his collaborators studied the effects and the mechanisms of the most common type of natural anthocyanidin, known as cyanidin-3-rutinoside, or C-3-R, which was extracted and purified from black raspberries, in several leukemia and lymphoma cell lines.
They found that the anthocyanin C-3-R caused about 50 percent of a human leukemia cell line known as HL-60 to undergo programmed cell death, or apoptosis, within about 18 hours of treatment at low doses. When they more than doubled the concentration of C-3-R, virtually all of the leukemia cells became apoptotic and died. Cyanidin-3-rutinoside also induced apoptosis in other human leukemia and lymphoma cell lines.
When the investigators studied the mechanism of cell death in the leukemia cells, they found that C-3-R induced the accumulation of peroxides, a highly reactive form of oxygen, which, in turn, activated a mitochondria-mediated apoptotic pathway. In contrast, when the researchers treated normal human blood cells with the C-3-R anthocyanidin, they did not find any increased accumulation of reactive oxygen species and there were no apparent toxic effects on these cells.
Previous studies have shown that the C-3-R anthocyanidin possesses strong antioxidant activities, a characteristic shared by other polyphenols, such as those found in green tea, which could be responsible for their chemoprevention effects. Dr. Yin’s work suggests that although C-3-R demonstrates antioxidant effects in the normal cells, it paradoxically induces an oxidative “stress” in the tumor cells. It is possible that this differential effect of C-3-R may account for its selective toxicity in the tumor cells.
According to Dr. Yin, these results indicate that C-3-R has the potential to be used in leukemia therapy with the advantages of being highly selective against cancer cells. “Because this compound is widely available in foods, it is very likely that it is not toxic even in purified form. Therefore, if we can reproduce these anti-cancer effects in animal studies, this will present a very promising approach for treating a variety of human leukemias and, perhaps, lymphomas as well.”
Editorial note: This type of information on anthocyanidins might also be useful someday to help create a broader polyphenol or flavonoid nutritional strategy for lowering the risk of many cancers. The American Cancer Society’s current recommendation to eat “5 a day” (or more) servings of fruits and vegetables is a fine start, as is the emphasis on eating a rainbow of colors. Knowing which phytochemicals are the most potent in terms of health is even better, so the food choices (or food extract supplement use) can be targetted for greater effect and general health benefit. The last step will be to discover synergistic combinations of polyphenols and other phytonutrients that offer the best disease prevention possible. It is known from in vitro (”test tube”) studies that combinations of flavonoids can be even more potent in killing some cancer cells than single flavonoids. This anthocyanidin study is an important contribution to our growing nutritional database regarding flavonoids, cancer, and health - Dr. Z.
Interesting points...
*A natural anthocyanidin found in many fruits and vegetables (as well as red wine) selectively kills leukemia cells...
*anthocyanidins - a group of natural flavonoids found in cherries, currants, blueberries, cranberries, red cabbage, and eggplant
*and in black raspberries
and also...
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'Superpill' could treat 2,000 genetic diseases
A radical new pill that could treat almost 2000 inherited diseases including some forms of cystic fibrosis and muscular dystrophy could be available within three years, scientists have said.
The drug is able to repair faulty genes in the body that lead to crippling illness, and is already in the early stages of human trials after promising results in mice. Scientists say that if the trials go well, it could be licensed as early as 2009.
The drug is unique because it can correct a mutation that leads to thousands of diseases.
Known as PTC124, it has already had encouraging results in patients with Duchenne muscular dystrophy and cystic fibrosis.
The pill works by effectively forcing the body to ignore genetic mutations, and to produce normal proteins, rather than the mutated versions which lead to disease. Patients would have to take it throughout their lives.
"There are literally thousands of genetic diseases that could benefit from this approach," Lee Sweeney, of the University of Pennsylvania, who is leading the research, said. "What's unique about this drug is it doesn't just target one mutation that causes disease, but a whole class of mutations."
Made by PTC Therapeutics, the pill has been staggeringly successful in animal models. A study published today in Nature magazine shows that in mice with a mutation that causes Duchenne muscular dystrophy, the drug starts dystrophin production and restores their muscles to health.
The research also suggests it should also work against more than 1,800 other genetic illnesses.
Experts today hailed the "wonder pill" as a major breakthrough.
Dr Marita Pohlschmidt, director of research at the Muscular Dystrophy Campaign, said the results were "very encouraging".
She said: "We look forward to the publication of the full results of these clinical trials so that we can see more clearly what the prospects and possible timescales are for treatment."
Posted: Thu Jun 07, 2007 12:37 pm Post Subject: Serious diseases genes revealed
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Serious diseases genes revealed
A major advance in understanding the genetics behind several of the world's most common diseases has been reported.
The landmark Wellcome Trust study analysed DNA from the blood of 17,000 people to find genetic differences.
They found new genetic variants for depression, Crohn's disease, coronary heart disease, hypertension, rheumatoid arthritis and type 1 and 2 diabetes.
The remarkable findings, published in Nature, have been hailed as a new chapter in medical science.
It is hoped they will pave the way for research into new treatments and genetic tests.
The £9m Wellcome Trust Case Control Consortium (WTCCC) involved 50 leading research groups analysing the DNA from 2,000 patients for each of the seven conditions and 3,000 healthy volunteers.
Genome-wide
They used "gene chips" to scan hundreds of thousands of DNA markers to identify common genetic differences across the whole genome.
Many of the genes identified by the team of 200 scientists were in parts of the genome not previously thought to be associated with disease.
In the future it may be possible to test people for combinations of genes to find out their lifetime risk of a disease, which would enable them to modify their lifestyle or undergo screening.
One of the most exciting finds was a previously unknown gene common to type 1 diabetes and Crohn's disease, a type of inflammatory bowel disorder, suggesting that they share similar biological pathways.
The team also unexpectedly found a process known as autophagy - a process of clearing bacteria from within cells - is important in the development of Crohn's disease.
And in type 1 diabetes, they identified several genetic regions that increase the risk of developing the condition.
The WTCCC project has already played a part in recent reports of an obesity gene, three new genes linked to type 2 diabetes, and a genetic region on chromosome 9 associated with coronary heart disease.
Major advances
Professor Peter Donnelly, chair of the WTCCC and professor of statistical science at Oxford University, said the research was a "new dawn" and they had learnt more in the past 12 months than they had in 15 years.
"If you think of the genome as very long road that you are trying to find your way along in the dark, previously we have only been able to turn lights on in a small number of places, but now we can turn on lights in a large number of places - in this case half a million lights."
"Many of the most common diseases are very complex, involving both 'nature' and 'nurture', genes interacting with our environment and lifestyles."
"By identifying the genes underlying these conditions, our study should enable scientists to understand better how disease occurs, which people are most at risk and, in time, to produce more effective, more personalised treatments."
Dr Mark Walport, director of the Wellcome Trust, added that all the data are being made publicly available to ensure that scientists across the globe have immediate access to the results.
"We have taken a big step forward in understanding the genetics underlying some of the most prevalent diseases affecting human health."
Matt Hunt, Science Information Manager at Diabetes UK, said: "The WTCCC has been an excellent example of collaborative working and has produced some exciting results about the genetics of Type 1 and Type 2 diabetes."
