ScienceDaily (Dec. 8, 2009) — A new study finds that compounds derived from the spices turmeric and pepper could help prevent breast cancer by limiting the growth of stem cells, the small number of cells that fuel a tumor’s growth.

Researchers at the University of Michigan Comprehensive Cancer Center have found that when the dietary compounds curcumin, which is derived from the Indian spice turmeric, and piperine, derived from black peppers, were applied to breast cells in culture, they decreased the number of stem cells while having no effect on normal differentiated cells.

“If we can limit the number of stem cells, we can limit the number of cells with potential to form tumors,” says lead author Madhuri Kakarala, M.D., Ph.D., R.D., clinical lecturer in internal medicine at the U-M Medical School and a research investigator at the VA Ann Arbor Healthcare System.

Cancer stem cells are the small number of cells within a tumor that fuel the tumor’s growth. Current chemotherapies do not work against these cells, which is why cancer recurs and spreads. Researchers believe that eliminating the cancer stem cells is key to controlling cancer. In addition, decreasing the number of normal stem cells — unspecialized cells that can give rise to any type of cell in that organ — can decrease the risk of cancer.

In this study, a solution of curcumin and piperine was applied to the cell cultures at the equivalent of about 20 times the potency of what could be consumed through diet. The compounds are available at this potency in a capsule form that could be taken by mouth.

The researchers applied a series of tests to the cells, looking at markers for breast stem cells and the effects of curcumin and piperine, both alone and combined, on the stem cell levels. They found that piperine enhanced the effects of curcumin, and that the compounds interrupted the self-renewal process that is the hallmark of cancer-initiating stem cells. At the same time, the compounds had no affect on cell differentiation, which is the normal process of cell development.

“This shows that these compounds are not toxic to normal breast tissue,” Kakarala says. “Women at high risk of breast cancer right now can choose to take the drugs tamoxifen or raloxifene for prevention, but most women won’t take these drugs because there is too much toxicity. The concept that dietary compounds can help is attractive, and curcumin and piperine appear to have very low toxicity.”

Curcumin and piperine have been explored by other researchers as a potential cancer treatment. But this paper, published online in the journal Breast Cancer Research and Treatment, is the first to suggest these dietary compounds could prevent cancer by targeting stem cells.

In addition, tamoxifen or raloxifene are designed to affect estrogen, which is a factor in most, but not all breast cancers. In fact, the aggressive tumors that tend to occur more often in women with a family history or genetic susceptibility are typically not affected by estrogen. Because curcumin and piperine limit the self renewal of stem cells, they would impact cancers that are not estrogen sensitive as well as those that are.

Researchers are planning an initial Phase I clinical trial to determine what dose of curcumin or piperine can be tolerated in people. The trial is not expected to begin accruing participants until spring.

Breast cancer statistics: 194,280 Americans will be diagnosed with breast cancer this year and 40,610 will die from the disease, according to the American Cancer Society

Additional authors include Dean Brenner, Hasan Korkaya, Connie Cheng, Karim Tazi, Christophe Ginestier, Suling Liu, Gabriel Dontu and Max Wicha, all from U-M

Funding was provided by the National Institutes of Health; curcumin and piperine were donated by Sabinsa Co.

Journal Reference:

1. Madhuri Kakarala, Dean E. Brenner, Hasan Korkaya, Connie Cheng, Karim Tazi, Christophe Ginestier, Suling Liu, Gabriela Dontu and Max S. Wicha. Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast Cancer Research and Treatment, 2009; DOI: 10.1007/s10549-009-0612-x

ScienceDaily (Dec. 9, 2009) — A new study has found that the amount of vitamin D in patients being treated for diffuse large B-cell lymphoma was strongly associated with cancer progression and overall survival. The results will be presented at the annual meeting of the American Society of Hematology in New Orleans.

“These are some of the strongest findings yet between vitamin D and cancer outcome,” says the study’s lead investigator, Matthew Drake, M.D., Ph.D., an endocrinologist at Mayo Clinic in Rochester. “While these findings are very provocative, they are preliminary and need to be validated in other studies. However, they raise the issue of whether vitamin D supplementation might aid in treatment for this malignancy, and thus should stimulate much more research.”

The researchers’ study of 374 newly diagnosed diffuse large B-cell lymphoma patients found that 50 percent had deficient vitamin D levels based on the commonly used clinical value of total serum 25(OH)D less than 25 ng/mL. Patients with deficient vitamin D levels had a 1.5-fold greater risk of disease progression and a twofold greater risk of dying, compared to patients with optimal vitamin D levels after accounting for other patient factors associated with worse outcomes.

The study was conducted by a team of researchers from Mayo Clinic and the University of Iowa. These researchers participate in the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE), which is funded by the National Cancer Institute. The 374 patients were enrolled in an epidemiologic study designed to identify predictors of outcomes in lymphoma. Since this was not a clinical trial, patient management and treatments were not assigned, but rather followed standard of care for clinical practice.

The findings support the growing association between vitamin D and cancer risk and outcomes, and suggest that vitamin D supplements might help even those patients already diagnosed with some forms of cancer, says Dr. Drake. “The exact roles that vitamin D might play in the initiation or progression of cancer is unknown, but we do know that the vitamin plays a role in regulation of cell growth and death, among other processes important in limiting cancer,” he says.

The findings also reinforce research in other fields that suggest vitamin D is important to general health, Dr. Drake says. “It is fairly easy to maintain vitamin D levels through inexpensive daily supplements or 15 minutes in the sun three times a week in the summer, so that levels can be stored inside body fat,” he says. Many physicians recommend 800-1,200 International Units (IU) daily, he adds.

Vitamin D is a steroid hormone obtained from sunlight and converted by the skin into its active form. It also can come from food (naturally or fortified as in milk) or from supplements. It is known best for its role of increasing the flow of calcium into the blood. Because of that role, vitamin D deficiency has long been known to be a major risk factor for bone loss and bone fractures, particularly in elderly people whose skin is less efficient at converting sunlight into vitamin D. But recent research has found that many people suffer from the deficiency, and investigators are actively looking at whether low vitamin D promotes poorer health in general.

Cancer researchers have discovered that vitamin D regulates a number of genes in various cancers, including prostate, colon and breast cancers. Recent studies have suggested that vitamin D deficiency may play a role in causing certain cancers as well as impacting the outcome once someone is diagnosed with cancer.

Researchers looked at vitamin D levels in lymphoma patients because of the observation, culled from U.S. mortality maps issued by the National Cancer Institute, that both incidence and mortality rates of this cancer increase the farther north a person lives in the United States, where sunlight is limited in the winter. Also, several recent reports have concluded that vitamin D deficiency is associated with poor outcomes in other cancers, including breast, colon and head and neck cancer. This is the first study to look at lymphoma outcome.

The study was funded by the National Cancer Institute and the Mayo Hematologic Malignancies Lymphoma Fund.