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Apigenin reduces progestin-driven breast tumor growth

Apigenin reduces progestin-driven breast tumor growth

Tuesday, May 22, 2012. Research described on May 9, 2012 in Hormones and Cancer reports that apigenin, a bioflavonoid that occurs in celery and other plants, helps reduce the growth of tumors fueled by a synthetic version of the hormone progesterone known as progestin. Progestins are included in drugs such as Prempro that are prescribed to women undergoing menopause to help relieve symptoms and protect the uterus from the hyperproliferative effects of estrogen replacement. Although it may help protect against endometrial cancer, progestin use has been associated with an increased risk of breast cancer.

The current research involved mice implanted with human breast cancer tumors that were positive for Her2/neu, a protein that appears on the surface of some breast cancer cells which correlates with increased aggressiveness and worse prognosis. Some of the animals were given medroxyprogesterone acetate (MPA), a progestin that is commonly prescribed to menopausal and postmenopausal women. The mice were then subdivided to receive apigenin by injection or no apigenin.

While mice that received MPA alone had a rapid rate of tumor growth, a slower rate occurred in those treated with apigenin, which was comparable to the rate observed in animals that did not receive MPA. Apigenin-treated animals also experienced tumor shrinkage, reduced expression of Her2/neu and lower levels of vascular endothelial growth factor.

"This is the first study to show that apigenin, which can be extracted from celery, parsley and many other natural sources, is effective against human breast cancer cells that had been influenced by a certain chemical used in hormone replacement therapy," announced lead researcher Salman M. Hyder of the University of Missouri's College of Veterinary Medicine and the Dalton Cardiovascular Research Center. "We don't know exactly how apigenin does this on a chemical level. We do know that apigenin slowed the progression of human breast cancer cells in three ways: by inducing cell death, by inhibiting cell proliferation, and by reducing expression of a gene associated with cancer growth. Blood vessels responsible for feeding cancer cells also had smaller diameters in apigenin-treated mice compared to untreated mice. Smaller vessels mean restricted nutrient flow to the tumors and may have served to starve the cancer as well as limiting its ability to spread."

"Clinical trials of apigenin with humans could start tomorrow, but we have to wait for medical doctors to carry out that next step," he added. "One problem is, because apigenin doesn't have a known specific target in the cancer cell, funding agencies have been reticent to support the research. Also, since apigenin is easily extracted from plants, pharmaceutical companies don't stand to profit from the treatment; hence the industry won't put money into studying something you can grow in your garden."

"Chemotherapy drugs cause hair-loss, extreme fatigue and other side effects," Dr Hyder noted. "Apigenin has shown no toxic side effects even at high dosages. People have eaten it since pre-history in fruits and vegetables."

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What's Hot Highlight

Red wine may be more protective than white wine against breast cancer

What's Hot

While increased alcohol intake in general has been associated with elevated breast cancer risk, the results of a study published online on December 7, 2011 in the Journal of Women's Health indicate that elements in red wine could be protective against the development of the disease. "Aromatase inhibitors prevent the conversion of androgens to estrogen and occur naturally in grapes, grape juice, and red, but not white wine," the authors note in their introduction to the article.

In a cross-over study, Glenn D. Braunstein, MD and his associates at Cedars-Sinai Medical Center in Los Angeles assigned 36 premenopausal women to eight ounces of red wine daily for one month followed by eight ounces of white wine for one month, or the reverse regimen. Blood samples collected at two points during the women's menstrual cycles were analyzed for the hormones estradiol, estrone, androstenedione, total and free testosterone, sex hormone binding globulin, luteinizing hormone and follicle stimulating hormone.

In addition to elevations of luteinizing hormone and free testosterone, the team found a small reduction in estrogen levels among participants who consumed red wine for one month in comparison with those who consumed white wine. In contrast, alcohol in general can increase estrogen levels, which fuels the most common type of breast cancer. "There are chemicals in red grape skin and red grape seeds that are not found in white grapes that may decrease breast cancer risk," stated Dr Braunstein, who is vice president for Clinical Innovation and the James R. Klinenberg, MD, Chair in Medicine at Cedars-Sinai.

"If you were to have a glass of wine with dinner, you may want to consider a glass of red," remarked study coauthor Chrisandra Shufelt, MD, who is an assistant director of the Women's Heart Center at the Cedars-Sinai Heart Institute. "Switching may shift your risk."

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