Beyond Broccoli: Cancer Focus Is on Food at Molecular Levels

The past decade has brought a significant increase in attention to the role that food and nutrients might play in fighting cancer. Media response to incremental news has sent consumers scurrying to eat more blueberries, cherries, tomatoes, broccoli, carrots, cranberries, and leafy green vegetables, and to drink green tea and red wine in hopes of warding off disease.

But whether these foods actually can help prevent cancer, or whether they are best utilized at the molecular level or in combination with other treatments once tumors have been discovered, are questions researchers are still exploring. Support for such research is on the rise, but results are coming in fits and starts as promising foods or nutrients become the latest favorites, stimulate controversy, or fade in the stretch.

Among the most promising studies are investigations into pomegranate juice that researchers at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles (UCLA) are conducting.

Allan Pantuck, MD, MS, director of Translational Research at the UCLA Kidney Cancer Program, is the principal investigator in a study in which it was found that drinking an 8-ounce glass of pomegranate juice each day increases by nearly 4-fold the period during which prostate specific antigen (PSA) levels remained stable in men being treated for prostate cancer.

Pomegranate juice is known to inhibit inflammation—which is thought to play a role in many cancers—and contains high levels of antioxidants, which are believed to protect the body from free-radical damage. Specifically, it contains polyphenols, natural antioxidant compounds found in green tea, as well as isoflavones commonly found in soy, and ellagic acid, which is believed to play a role in cancer cell death.

The findings might prove particularly helpful amid the uncertainty that persists over the precise implications of rising PSA levels. Currently, there is no standard treatment for men who have recurrent prostate cancer detected by an increase in PSA level only, according to the National Cancer Institute (NCI).¹

Allan Pantuck, MD, MS, is investigating the influence of pomegranate juice on PSA levels in a phase III trial.

“In a phase II trial we conducted, daily consumption of pomegranate juice resulted in a significant lengthening of PSA doubling time and disease stabilization,” said Pantuck.

In that phase II Simon 2-stage clinical trial, men with rising PSA levels after surgery or radiotherapy were treated. Eligible patients had a detectable PSA >0.2 and <5 ng/mL and Gleason score of v7. Patients were treated with 8 ounces of pomegranate juice daily (Wonderful brand, 570 mg total polyphenol gallic acid equivalents) until disease progression. Clinical endpoints included safety and effect on serum PSA, serum-induced proliferation, and apoptosis of human prostate cancer (LNCaP) cells, serum lipid peroxidation, and serum nitric oxide levels.²

Researchers are now conducting a phase III, double-blinded, placebo-controlled study that is one of the most advanced of the current food and nutrient clinical trials, Pantuck said.

Drinking a glass of pomegranate juice or taking a pill each day “would be ideal” as a treatment with minimal side effects, he said.

Pantuck is sufficiently impressed by the results that he has added pomegranate juice to his own diet several times a week as part of his personal practice of eating a rainbow of foods. “I try to eat what I call a colorful diet,” he said, in keeping with the belief that the substances that give color to a food are an indicator of the antioxidants contained within.

Pomegranate also is being investigated as a possible treatment for breast cancer, heart disease, and other health issues, he said.

Marilene Beth Wang, MD, is studying the interaction of curcumin and cisplatin.

Out of the Kitchen Cabinet

Elsewhere at UCLA, Marilene Beth Wang, MD, is lead author of a study of curcumin, the major component in the spice turmeric. Curcumin has been found to enhance chemotherapy’s ability to suppress head and neck cancer cell growth when combined with the drug cisplatin.

Turmeric is among the many spices and foods that have been used throughout history by healers; it is widely used in South Asian and Middle Eastern cooking, and is credited with having anti-inflammatory effects. In India, women use it as an antiaging agent rubbed into their skin and as a poultice to promote wound healing.

However, the amount of curcumin needed to produce a clinical response—about 500 mg—would be much larger than the amount in turmeric used in cooking.

Previous studies have shown curcumin can suppress the growth of certain cancers, said Wang, who became involved in the study through her role as a head and neck surgeon at the UCLA School of Medicine.

“The treatments for head and neck cancer are far from ideal,” she said. “Head and neck cancers, particularly cases diagnosed in a later stage, are terrible cancers that require very radical surgeries and chemotherapy and radiation. They often don’t present until late, and the structures in the head and neck are so vital that our treatments often cause disfigurement and severe loss of function. So using nontoxic curcumin as a treatment was a very appealing idea.”

The study, performed in cells in Petri dishes and then in mouse models, appeared in the October issue of the journal Molecular Cancer Therapeutics.

In the animal studies, the curcumin was applied directly onto the tumors in paste form because it did not dissolve in saline, which would have allowed it to be injected.

Pomegranate juice, prepared (below) by a street vendor in Turkey, helped stabilize PSA levels in a phase II trial.

In need of a better way to deliver the curcumin, Wang and collaborator Eri Srivatsan, PhD, worked with Kapil Mehta, PhD, professor in the Department of Experimental Therapeutics, Cancer Medicine, at the University of Texas MD Anderson Cancer Center in Houston. They found that encapsulating the curcumin in a liposome made the treatment injectable.

The goal was to combine curcumin with cisplatin, which is highly toxic at the doses needed to fi ght head and neck cancers, causing damage to kidneys, ears, and bone marrow. With curcumin, they wanted to be able to lower the cisplatin dose and lessen organ damage. Their finding, that curcumin made cisplatin more effective, was very promising, Wang said.

The future may bring a product that patients could chew, she said. “By chewing on curcumin, it could have an effect by coming in contact with the cancer.”

The next step will be to test curcumin on human beings. Patients scheduled for treatment will take curcumin every day, and then the surgeon will conduct a biopsy to see whether there is any change. The trials have been approved for the clinical stage and the researchers are awaiting word on a grant.

Curcumin also has shown a suppressive effect on breast, colon, and pancreatic cancers, Wang said.

Scott D. Cramer, PhD, is researching stem cell targets for vitamin D.

Areas of Exploration Are Expanding

Research into the connection between nutrition and cancer continues to grow. Between 2008 and 2009, the NCI increased the number of nutrition grants awarded by 24%, from 491 to 608. Research project grants increased 9% and exploratory/developmental grants increased 40%. Program project grants more than doubled.³

Last year, the NCI offered grants of up to $275,000 over 2 years to support exploratory molecular research into the bioactive components in food and in diets that have been shown to alter tumor behavior.

But the search for foods or components that can protect against cancer is not limited to items found at the supermarket.

Scott D. Cramer, PhD, is working on the study of the prostate stem cell as a target of vitamin D chemoprevention. He is a professor of cancer biology at the Comprehensive Cancer Center and Center for Cancer Genomics, Urology, Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Vitamin D has received much media attention in recent years and been touted at times as a possible treatment for a host of major diseases. Recently issued Institute of Medicine guidelines on recommended levels have spurred some controversy, but after 20 years of studies, Cramer remains convinced it is a powerful source of preventive medicine.

His studies focus on circulating vitamin D levels as they are inversely associated with prostate cancer risk and supplementation with vitamin D for prostate cancer prevention with a goal of developing chemoprevention strategies for prostate cancer.⁴

“It’s clear that people are not getting as much vitamin D as they did in the past,” he said. “When we were naked in the savannah, our bodies adapted to a much higher amount of vitamin D than we now have.”

He said there is no doubt that prostate cancer risk is associated with sun exposure.

“People who live farther away from the equator have a higher prostate cancer risk,” he said.

It also is becoming increasingly clear that many people, especially the elderly, have vitamin D deficiencies. For the elderly, that is partly because their skin becomes thinner as they age and they are less able to make vitamin D through sun exposure. In those cases, he recommends supplements.

“This is a super-cheap, readily available, and safe dietary supplement,” he said.

But he sees vitamin D’s greatest power as a preventive, he said. “The real benefit is getting our children off to the right start.”

Cramer said he takes a vitamin D supplement, but that his children do not require one as long as they spend enough time in the sunshine without sunscreen.

Vitamin D is also being investigated as a potential breast cancer preventive and as a means of warding off the return or spread of lung cancer after surgery.

Robin McConnell, MS, RD, crafts nutrient-rich diets for cancer survivors at the John Theurer Cancer Center in New Jersey.

An Ounce of Prevention

While many questions about the role food and nutrients play in cancer remain unanswered, there is growing awareness about the importance of nutrition for cancer survivors.

According to the NCI, early recognition and detection of risk for malnutrition through screening and comprehensive assessment is increasingly recognized as imperative in the development of quality-care standards in oncology practices.⁵

Malnutrition is cited as a component in many cancer deaths, including among the elderly, who often eat less as they age. Cachexia, a progressive wasting syndrome, is estimated to be the immediate cause of death in 20% to 40% of cancer patients.⁵

Robin McConnell, MS, RD, clinical nutrition coordinator at John Theurer Cancer Center at Hackensack University Medical Center in New Jersey, is familiar with the nutritional challenges that face patients at all stages of treatment and recovery.

As a registered dietitian specialist in oncology nutrition, she and other members of the staff at Theurer work with patients primarily in treatment. Due to depression, altered taste, anorexia, surgery, or an inability to process food, “People have tremendous issues with eating,” she said.

References

1. Pomegranate juice for PSA-only prostate cancer recurrence. National Cancer Institute Website. www.cancer.gov. Published September 25, 2007. Updated March 16, 2010. Accessed May 3, 2011.
2. Pantuck AJ, Leppert JT, Zomorodian N, et al. Phase II study of pomegranate juice for men with rising prostate-specifi c antigen following surgery or radiation for prostate cancer. Clin Cancer Res. 2006;12(13):4018-4026. doi: 10.1158/1078-0432.CCR-05-2290.
3. Nutritional Science Research Group. NCI nutrition grants. Nutrition Frontiers. Bethesda, MD: National Cancer Institute, Division of cancer Prevention. Nutrition Frontiers. Nutritional Science Research Group newsletter. 2010: 1(4). Accessed May 3, 2011.
4. Research Portfolio Online Reporting Tools (RePORT). Bethesda, MD: National Institutes of Health. RePORT Accessed May 3, 2011.
5. Nutrition in cancer care PDQ. National Cancer Institute Website. Nutrition in Cancer Care. Updated December 9, 2010. Accessed May 3, 2011.

By crafting nutrient-dense diets for patients “we see people gain weight because they are able to utilize the food they eat. We take the chemistry of nutrition and package it in foods that the patient can eat.”

Always, they are looking at the long term for cancer survivors.

“I found that people are extremely receptive to nutrition intervention once they have a diagnosis of cancer. They are really looking for knowledge,” McConnell said.

At that point in their illness, so much is out of control for the patient, but “when you have cancer you can take over this aspect of your life. It gives them some control in an uncontrollable situation.”

Changing to a healthy, plant-based diet, low in animal fats and high in grains, also supports long-term survival, she said, especially for patients with other diseases such as diabetes.

“A healthy diet is a healthy diet. People can be healthier after cancer treatment than when they started,” she said.

An added bonus is when cancer survivors offer their knowledge to the next generation.

“Parents set good examples for their families. They take what they learn home with them, which is helpful for prevention. When you see someone coming out of cancer more healthy, that’s a powerful message,” she said.

Her advice for using food as a healthy way to prevent illness echoes Pantuck’s.

“Fill your plate with color,” she said. “Not only is it more visually appealing, it’s better for you.”