UA Discovery Shows Curcumin Blocks the Metastasis of Colon Cancer by a Novel Mechanism

A team of researchers led by the University of Arizona Steele Children’s Research Center discovered that curcumin—the bioactive molecule derived from the spice turmeric—blocks the protein cortactin in colon cancer.

Cortactin, a protein essential for cell movement, frequently is overexpressed in cancer, thus facilitating cancer cell metastasis to other organs in the body.

Colon cancer is the second leading cause of cancer-related deaths in the United States and the third most common cancer in men and women. When cancer metastasizes to other organs, a patient’s chances of survival are greatly diminished. Thus, finding novel ways to prevent cancer metastasis remains an urgent need.

The National Institutes of Health-funded research  recently was published in PLOS One (available here).

The study was led by co-investigators Fayez K. Ghishan, MD, professor and head, UA Department of Pediatrics and director of the UA Steele Children’s Research Center; Pawel Kiela, DVM, PhD, associate professor, UA Department of Pediatrics; and Vijay Radhakrishnan, PhD, assistant scientist, UA Department of Pediatrics. The study was conducted in collaboration with Jessie Martinez, PhD, professor, UA Cancer Center, and Eugene Mash, PhD, professor, Department of Chemistry and Biochemistry.

Turmeric gives curry its yellow color and flavor. It is part of the ginger family and has been used for thousands of years to treat colds, inflammation, arthritis and many other ailments, including cancer.

Curcumin is the active ingredient in turmeric and has been scientifically studied in many types of cancer. It has been shown to have a chemopreventative effect—the ability to reverse, suppress or prevent the development of cancer.

“What’s novel about our research is that our study identified one of the mechanisms by which curcumin can prevent cancer cell metastasis in colon cancer,” said Dr. Ghishan.

The research team discovered that the active part of the cortactin protein, known as Phopsho Tyrosine 421 (pTyr421), is hyper-activated in malignant tumors of the colon.

“We showed that the cortactin protein was hyper-activated due to a process called excessive phosphorylation,” said Dr. Kiela.

Phosphorylation is the addition of a phosphate group to a protein, and is responsible for turning proteins on and off, altering the protein’s function and activity. Too much cortactin, and its activation by phosphorylation, has been linked with cancer aggressiveness.

The researchers treated human colon cancer tumor cells with curcumin. “We discovered that curcumin turns off the active form of cortactin,” explained Dr. Radhakrishnan, who led the experiments in the lab. “Thus, when cortactin is turned off, cancer cells lose the ability to move and can’t metastasize to other parts of the body.”

More specifically, curcumin “turned-off” cortactin by interacting with, and activating, an enzyme known as PTPN1. This enzyme acts as a phosphatase to remove phosphate groups from cortactin—a process known as “dephosphorylation.”

“This effect, essentially known as ‘dephosphorylating cortactin’ correlated with reduced ability of colon cancer cells to migrate,” said Dr. Kiela. “This suggests that curcumin reduces cancer cells’ ability to migrate, meaning the cancer can’t metastasize.”

“By identifying the mechanism of action—that curcumin activates the enzyme PTPN1, which then ‘turns off’ the active component of cortactin pTyr421, we believe that chemopreventative drugs can be developed to target cortactin in cancer cells to prevent the cancer from metastasizing,” said. Dr. Radhakrishnan.

“Treatments aimed at the suppression of cancer metastasis remain an urgent therapeutic need,” said Dr. Ghishan. “Our findings have laid the foundation for future research to develop treatments using curcumin to prevent cancer’s deadly spread to other organs.”
This study was funded by NIH grant No.  5 R01 DK067286.  Additional contributors to the study included Pawel Kojs, BS, UA Department of Nutritional Sciences; Gavin Young, BS, University of Arizona Cancer Center; Raji Ramalingam, PhD, UA Department of Pediatrics; Bhumasamudram Jagadish, PhD, University of Arizona Cancer Center and Department of Chemistry and Biochemistry.

The UA Steele Children’s Research Center is one of the prestigious Centers of Excellence within the UA College of Medicine – Tucson. It is the only facility in Southern Arizona where researchers and physician-scientists are dedicated to advancing medical knowledge through research to improve children’s health. As researchers, they seek to discover answers to children’s medical mysteries. As physician-scientists, they provide compassionate care to hospitalized patients at the University of Arizona Medical Center –  Diamond Children’s and pediatric outpatient clinics throughout Tucson and the state. And, as faculty members with the UA Department of Pediatrics, they teach and train the next generation of pediatricians and researchers.