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Colorful Berry Pigment Kills Leukemia
4/26/2007
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Antioxidant food factor in raspberries, strawberries, grapes, and tart cherries kills cancer cells via multiple means

by Craig Weatherby


Berries and other colorful fruits are abundant in the beneficial antioxidant compounds called polyphenols, many of which also function as bright pigments.


Most plant polyphenols demonstrate beneficial cardiovascular and anti-cancer effects in test tube and animal tests.


Leukemia: less common than
other cancers, but more dangerous

According to the Leukemia & Lymphoma Society, some 35,000 new cases of leukemia were diagnosed in the United States in 2006.


This makes leukemia much less common than breast, lung, colon, or prostate cancers, but what it lacks in numbers, this class of cancers makes up for in insidiousness.


Survival rates vary widely by type of leukemia, but the average five-year survival rate for leukemia ranks much lower than those for breast or colon cancer, with just under half of all patients enduring for five years.


More than half of all cases occur after age 64, with men accounting for more than 57 percent of leukemia cases.


While leukemia strikes nine times as many adults as children, it constitutes a whopping one-third of cancers in children aged 0-14 years.


Signs of acute leukemia may include blood-related symptoms such as easy bruising or bleeding, paleness or easy fatigue, recurrent minor infections, or poor healing of minor cuts.

These findings dovetail with population studies that link higher intake of colorful fruits and vegetablesand of whole grains, which are also high in polyphenolsto lower rates of cancer and heart disease.


Anthocyaninsthe antioxidant pigments that turn autumn leaves red and purplerank high among the many kinds of beneficial polyphenols.


The richest food sources of anthocyanins include blueberries, strawberries, raspberries, tart cherries, cranberries, currants, grapes, pomegranate, and acai (ah-sigh-yee): an Amazonian fruit.


Anti-cancer findings reported this week serve to make the delicious fruit sources of anthocyanin-type polyphenols even more attractive.


The new findings focus on a particular anthocyanin, found most abundantly in raspberries, strawberries, grapes, and tart cherries.


All of these reddish fruits are rich in a particular anthocyanincalled cyanidin-3-rutinosidethat appears to exert powerful preventive effects against leukemia: impacts that also suggest possible therapeutic promise.


Pittsburgh team uncovers anti-leukemia power in red-purple foods

Researchers at the University of Pittsburgh wanted to see what would happen to human leukemia cells exposed to a particular anthocyanin abundant in raspberries, strawberries, grapes, and cherries (Feng R et al 2007).


His team’s motivation was expressed by co-author Xiao-Ming Yin, M.D., Ph.D.: “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” (University of Pittsburgh 2007).


They exposed several leukemia and lymphoma cell lines to cyanidin-3-rutinoside, which is among the most common types of anthocyanin, extracted in this case from black raspberries.


They reported that cyanidin-3-rutinoside induced apoptosis (cellular suicide) in leukemia cells of the HL-60 type. The killing effect was clearly due to the anthocyanin alone, since it destroyed cancer cells to degrees of effectiveness that varied by the dose.


Paradoxically, even though this anthocyanin compound generally acts as a potent antioxidant, it killed the cancer cells in part by acting as a “pro-oxidant” agent.


Specifically, it generated the peroxide free radicals which stimulates the leukemia cells to commit suicide. These are the same kind of free radicals that certain human immune-system cells use to kill bacteria.


The potent berry pigment also activated genetic switches called p38 MAPK and JNK, which facilitated increased suicide rates among the human leukemia cells.


Better yet, the anthocyanin compound had no toxic effects on normal blood cells.


As the researchers said, “These results indicate that cyanidin-3-rutinoside [has] the promising potential to be used in leukemia therapy with the advantages of being widely available and being selective [in acting only] against tumors” (Feng R et al 2007).


In other words, berries may offer chemotherapeutic benefits, without the adverse effects associated with most chemotherapy drugs.


The caveat, of course, is that these results need to be confirmed in animal tests, then in humans.


The broadly positive record from animal tests make it clear that raspberries, strawberries, blueberries, tart cherries, cranberries, currants, grapes, and other red-purple fruits offer significant protection against cancer in general, and may also aid in treating tumors.



Sources

  • Chen F, Sun Y, Zhao G, Liao X, Hu X, Wu J, Wang Z. Optimization of ultrasound-assisted extraction of anthocyanins in red raspberries and identification of anthocyanins in extract using high-performance liquid chromatography-mass spectrometry. Ultrason Sonochem. 2007 Jan 20; [Epub ahead of print]
  • Chen PN, Chu SC, Chiou HL, Kuo WH, Chiang CL, Hsieh YS. Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line. Cancer Lett. 2006 Apr 28;235(2):248-59. Epub 2005 Jun 22.
  • Feng R, Ni HM, Wang SY, Tourkova IL, Shurin MR, Harada H, Yin XM. Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress. J Biol Chem. 2007 Mar 20; [Epub ahead of print]
  • Garcia-Alonso M, Rimbach G, Rivas-Gonzalo JC, De Pascual-Teresa S. Antioxidant and cellular activities of anthocyanins and their corresponding vitisins A--studies in platelets, monocytes, and human endothelial cells. J Agric Food Chem. 2004 Jun 2;52(11):3378-84.
  • Lopes-da-Silva F, Pascual-Teresa SD, Rivas-Gonzalo JC, Santos-Buelga C. Identification of anthocyanin pigments in strawberry (cv Camarosa) by LC using DAD and ESI-MS detection. European Food Research and Technology. Issue Volume 214, Number 3 / March, 2002. DOI 10.1007/s00217-001-0434-5; Pages 248-253.
  • Seeram NP, Bourquin LD, Nair MG. Degradation products of cyanidin glycosides from tart cherries and their bioactivities. J Agric Food Chem. 2001 Oct;49(10):4924-9.
  • Seeram NP, Momin RA, Nair MG, Bourquin LD. Cyclooxygenase inhibitory and antioxidant cyanidin glycosides in cherries and berries. Phytomedicine. 2001 Sep;8(5):362-9.
  • Shih PH, Yeh CT, Yen GC. Effects of anthocyanidin on the inhibition of proliferation and induction of apoptosis in human gastric adenocarcinoma cells. Food Chem Toxicol. 2005 Oct;43(10):1557-66.
  • Tian Q, Giusti MM, Stoner GD, Schwartz SJ. Urinary excretion of black raspberry (Rubus occidentalis) anthocyanins and their metabolites. J Agric Food Chem. 2006 Feb 22;54(4):1467-72.
  • University of Pittsburgh. A Natural Antioxidant Found in Many Foods and Red Wine Is Potent and Selective Killer of Leukemia Cells: University of Pittsburgh Researchers Show Compound Kills Leukemia Cells While Sparing Normal, Healthy Cells. Accessed online April 24, 2007 at http://upmc.com/Communications/NewsBureau/NewsReleaseArchives/2007/April/YinLeukemiaStudy.htm
  • Yeh CT, Yen GC. Induction of apoptosis by the Anthocyanidins through regulation of Bcl-2 gene and activation of c-Jun N-terminal kinase cascade in hepatoma cells. J Agric Food Chem. 2005 Mar 9;53(5):1740-9. 

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