Tag Archives: PLOS ONE

cancer

UA Shows Curcumin Effect on Colon Cancer

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.

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.”

banner alzheimers foundation - brain research

Combination of Diet and Radiation Therapy Shows Promise

A team of brain cancer researchers at Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center has effectively treated brain tumor cells using a unique combination of diet and radiation therapy. The study, “The Ketogenic Diet Is an Effective Adjuvant to Radiation Therapy for the Treatment of Malignant Glioma,” was published in PLOS ONE.

Led by Adrienne C. Scheck, PhD, Principal Investigator in Neuro-Oncology and Neurosurgery Research at Barrow, the groundbreaking research studied the effects of the ketogenic diet in conjunction with radiation therapy for the treatment of malignant gliomas, an aggressive and deadly type of brain tumor. The ketogenic diet is a high-fat, low-carbohydrate diet that alters metabolism and is used in the treatment of pediatric epilepsy that does not respond to conventional therapies. The diet’s affects on brain homeostasis have potential for the treatment of other neurological diseases, as well.

In the study, mice with high-level malignant gliomas were maintained on either a standard or a ketogenic diet. Both groups received radiation therapy. Dr. Scheck’s team discovered that animals fed a ketogenic diet had an increased median survival of approximately five days relative to animals maintained on a standard diet. Of the mice that were fed a ketogenic diet and received radiation, nine of 11 survived with no signs of tumor recurrence, even after being switched back to standard food, for over 200 days. None on the standard diet survived more than 33 days.

One theory behind the success of the treatment is that the ketogenic diet may reduce growth factor stimulation, inhibiting tumor growth. Barrow scientists also believe that it may reduce inflammation and edema surrounding the tumors. This is believed to be the first study of its kind to look at the effects of the ketogenic diet with radiation.

Dr. Scheck believes that the study has promising implications in the treatment of human malignant gliomas. “We found that the ketogenic diet significantly enhances the anti-tumor effect of radiation, which suggests that it may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas,” she says.

Dr. Scheck adds that the ketogenic diet could quickly and easily be added into current brain tumor treatment plans as an adjuvant therapy without the need for FDA approval. She is currently exploring options for clinical trials.