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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.”

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Cutting Your Cancer Risk

Picture yourself in a room of 20 people.

Of these 20 people, one will develop colorectal cancer in his/her lifetime.
“Colon cancer is among the most common cancers diagnosed in this country, with more than 100,000 new cases each year,” said Dr. Murali Murty of Arizona Center for Cancer Care in Scottsdale. “What’s more, it is the third leading cause of cancer-related deaths with the American Cancer Society reporting there may be as many as 50,000 Americans losing their lives to this disease this year alone.”
But, this number need not be so staggering.
“Education on the disease, coupled with proactive methods for early detection and new treatment advances, can greatly reduce this number on a local and national level,” said Dr. Murty.

What is colon cancer?

Colon cancer is cancer of the large intestine. It is often found to be present along with cancer of the rectum, and is then referred to as colorectal cancer. Cancer that begins in the lining of 153010495the colon, or adenocarcinoma, accounts for over 90 percent of all colon cancer cases. In almost 100 percent of cases, the cancer starts as a polyp on the colon.

Who is at risk?

Colon cancer is color blind – meaning all races and ethnicities are at risk. And, while commonly thought to be a disease limited to males, it is just as easy for women to develop. Additional risks, according to Dr. David S. Mendelson of Pinnacle Oncology Hematology in Scottsdale, include:

• Age – those over 50
• Diet – those who are overweight, lacking in fiber and/or overindulging in alcohol
• Family history – those who have family members diagnosed with the disease
• Lack of exercise – those who don’t get enough cardiovascular exercise on most days of the week
• Smoking – long-term smoking increases one’s risk of nearly every kind of disease on the planet

Symptoms

“The bad news is that in its earliest – and more treatable stages – there aren’t apparent symptoms,” said Dr. Murty.
This is the No. 1 reason screening tests are critical.
“When we do start to see symptoms, which can include blood in the stool, chronic stomach cramps and unexplained weight loss, the cancer may have already reached a later stage,” said Dr. Mendelson.

Early detection

As Katie Couric has taught us, both men and women should get their first colonoscopy by age 50, and should repeat the process as requested by one’s medical professional, usually once every five to 10 years. A colonoscopy involves the insertion of a thin tube into one’s rectum by a medical professional to check the colon for any polyps or other growths that might be dangerous.
“And yes, you are sedated when this happens, so it is not nearly as scary as it sounds,” said Dr. Mendelson. “Other diagnostic tools may include blood tests, x-rays and/or CT scans.”
One should begin the screening process earlier if he or she has any family history of the disease or other GI-related issues, such as Irritable Bowel Syndrome.

Treatment

“Once the actual cancer is diagnosed, the next step is determining the stage and then usually the surgical removal of the cancer,” said Dr. Mendelson.
Chemotherapy or radiation therapy may be used in addition to surgery to treat the cancer, especially if it has spread to other areas of the body.
“Due to advances in treatment of colorectal cancer, more patients are spared the complete removal of anus and rectum these days. This means fewer patients need a colostomy bag. Generally, chemotherapy and radiation are given first to help shrink the rectal tumor,” said Dr. Murty.
After this, surgeons have a better chance of removing only the part of the rectum with the tumor and sparing the anus, which allows normal bowel function. In very early rectal cancers, surgeons may be able to remove the tumor with no additional chemotherapy or radiation at all.
“However, when required, radiation is much more tolerable and has far fewer side effects, thanks to technological advances in recent years,” said Dr. Murty.

Prevention

173329702The general rule of thumb is to start a cardiovascular exercise routine, quit and/or avoid smoking as well as avoid secondhand smoke and to take a good, hard look at one’s diet.
“We are forgetting to feed our colons, while polluting our bodies with useless junk,” said Dr. Frank W. Jackson of Jackson GI Medical. “Fiber, in particular, is lacking in virtually all American diets.”
And it shows.
“We tend to ignore how fiber and its ability to fuel the glorious cauldron of bacteria in our colons, which is quietly amongst our most powerful health organs, can help prevent disease,” said Dr. Jackson, who recommends prebiotic fibers, which help to feed the good bacteria in one’s colon, fueling its war against the bad, cancer-causing bacteria also present.
However, Americans are really only getting this critical fiber via wheat and onions; Europeans, on average, consume five times the amount daily.  As a result, many are turning to prebiotic supplement programs, like Prebiotin, readily available at most vitamin and health stores – and even Sprouts – in the area.