Early Study Shows Spice Stunts Deadly Spread To Lungs

The study, to be published in the Oct. 15 issue of the journalClinical Cancer Research, reports that the spice appears to shut down aprotein active in the spread of breast cancer to a major target formetastasis.

Though the study results are early, researchers foundthat the nontoxic natural substance not only repelled progression ofthe disease to the lungs, but also appeared to reverse the effects ofpaclitaxel (TaxolTM),a commonly prescribed chemotherapy for breast cancer that may triggerspread of the disease with use over a long period of time.

Because Taxol is so toxic, it activates a protein that produces aninflammatory response that induces metastasis. Curcumin suppresses thisresponse, making it impossible for the cancer to spread. In fact,researchers found that adding curcumin to Taxol actually enhances itseffect. Curcumin breaks down the dose, making the therapy less toxicand just as powerful while delivering the same level of efficacy.

"We are excited about the results of the study and the possibleimplications for taking the findings into the clinic in the nextseveral years," says Bharat Aggarwal, Ph.D., professor of cancermedicine in M. D. Anderson's Department of Experimental Therapeutics."At this time, advanced breast cancer is a difficult foe to fight withfew proven treatments available after surgery, chemotherapy andradiation therapy."

Taxol is currently used as the front-line chemotherapeuticagent in breast cancers, but because the drug frequently induces drugresistance after prolonged use, it is not effective in treatingmetastatic breast cancer, says Aggarwal.

Researchers studied 60 mice with breast cancer, which wererandomly assigned to one of four groups: control group, Taxol only,curcumin only and the combination of Taxol and curcumin. After thetumors grew to 10 mm (about the size of a pea), they were surgicallyremoved, and the mice were fed a powdered curcumin diet.

Macroscopic lung metastasis, or metastasis that is visible to the nakedeye, was seen in 96 percent of the mice in the control group. Treatmentusing 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 lungmetastases.

Microscopic metastasis, or metastasis that is visible only when using amicroscope, was found in the lungs of 28 percent of mice treated withthe combination of curcumin and Taxol, and there was no macroscopicdisease present. The micrometastases present consisted of only a fewcells, suggesting that the combination inhibited the growth of breastcancer tumor cells that were in the lung before the tumors wereremoved.

In a previous study published in the Aug. 15 issue of thejournal Cancer, M. D. Anderson researchers found that when the nuclearfactor-kappa B (NF-kB) (a powerful protein known to promote theinflammatory response necessary to cause breast cancer to spread) isshut down, cancer strains are unable to grow and cells are pushed tocommit suicide.

The mechanism in this curcumin study works the same way. Taxolactivated the NF-kB in breast cancer cells, while curcumin stopped thisactivation by blocking the protein known as "IKK" that switched on theNF-kB, demonstrating how curcumin and Taxol work against one another.Taxol produced the inflammatory response, triggering metastasis, andcurcumin suppressed it, causing cell death.

Extracted from the roots of the curcuma longa plant, curcuminis a member of the ginger family. While it is not used in conventionalmedicine, it is widely prescribed in Indian medicine as a potent remedyfor liver disorders, rheumatism, diabetic wounds, runny nose, cough andsinusitis. Traditional Chinese medicine uses curcumin as a treatmentfor diseases associated with abdominal pain, and it is used in ancientHindu medicine as a treatment for sprains and swelling.

According to the American Cancer Society, the chance of a womanhaving invasive breast cancer sometime during her life is one in eight.About 211,240 women in the United States will be diagnosed withinvasive breast cancer in 2005, and approximately 40,410 women will diefrom 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.