The study, to be published in the Oct. 15 issue of the journal Clinical Cancer Research, reports that the spice appears to shut down a protein active in the spread of breast cancer to a major target for metastasis.
Though the study results are early, researchers found that the nontoxic natural substance not only repelled progression of the disease to the lungs, but also appeared to reverse the effects of paclitaxel (Taxol
Because Taxol is so toxic, it activates a protein that produces an inflammatory response that induces metastasis. Curcumin suppresses this response, making it impossible for the cancer to spread. In fact, researchers found that adding curcumin to Taxol actually enhances its effect. Curcumin breaks down the dose, making the therapy less toxic and just as powerful while delivering the same level of efficacy.
"We are excited about the results of the study and the possible implications for taking the findings into the clinic in the next several years," says Bharat Aggarwal, Ph.D., professor of cancer medicine in M. D. Anderson's Department of Experimental Therapeutics. "At this time, advanced breast cancer is a difficult foe to fight with few proven treatments available after surgery, chemotherapy and radiation therapy."
Taxol is currently used as the front-line chemotherapeutic agent in breast cancers, but because the drug frequently induces drug resistance after prolonged use, it is not effective in treating metastatic breast cancer, says Aggarwal.
Researchers studied 60 mice with breast cancer, which were randomly assigned to one of four groups: control group, Taxol only, curcumin only and the combination of Taxol and curcumin. After the tumors grew to 10 mm (about the size of a pea), they were surgically removed, and the mice were fed a powdered curcumin diet.
Macroscopic lung metastasis, or metastasis that is visible to the naked eye, was seen in 96 percent of the mice in the control group. Treatment using Taxol alone only "modestly reduced" the incidence of metastases, while the group using curcumin alone and curcumin plus Taxol "significantly reduced" both the incidence and numbers of visible lung metastases.
Microscopic metastasis, or metastasis that is visible only when using a microscope, was found in the lungs of 28 percent of mice treated with the combination of curcumin and Taxol, and there was no macroscopic disease present. The micrometastases present consisted of only a few cells, suggesting that the combination inhibited the growth of breast cancer tumor cells that were in the lung before the tumors were removed.
In a previous study published in the Aug. 15 issue of the journal Cancer, M. D. Anderson researchers found that when the nuclear factor-kappa B (NF-kB) (a powerful protein known to promote the inflammatory response necessary to cause breast cancer to spread) is shut down, cancer strains are unable to grow and cells are pushed to commit suicide.
The mechanism in this curcumin study works the same way. Taxol activated the NF-kB in breast cancer cells, while curcumin stopped this activation by blocking the protein known as "IKK" that switched on the NF-kB, demonstrating how curcumin and Taxol work against one another. Taxol produced the inflammatory response, triggering metastasis, and curcumin suppressed it, causing cell death.
Extracted from the roots of the curcuma longa plant, curcumin is a member of the ginger family. While it is not used in conventional medicine, it is widely prescribed in Indian medicine as a potent remedy for liver disorders, rheumatism, diabetic wounds, runny nose, cough and sinusitis. Traditional Chinese medicine uses curcumin as a treatment for diseases associated with abdominal pain, and it is used in ancient Hindu medicine as a treatment for sprains and swelling.
According to the American Cancer Society, the chance of a woman having invasive breast cancer sometime during her life is one in eight. About 211,240 women in the United States will be diagnosed with invasive breast cancer in 2005, and approximately 40,410 women will die from the disease this year.
The study was funded by the United States Department of Defense. Co-authors include Shishir Shishodia, Ph.D.; Yasunari Takada, Ph.D.; Sanjeev Banerjee, Ph.D.; Robert A. Newman, Ph.D.; Carlos Bueso-Ramos, M.D., Ph.D.; and Janet E. Price, Ph.D.
Clinical Cancer Research