The process of enhancing cancer cells' susceptibility to therapeutic treatments is known as sensitization. With funding from AICR, researchers are finding that dietary compounds may play a key role in this relatively new field.
In the field of sensitization, studies are burgeoning about the potential for improving conventional cancer treatment by adding components from soy, grape seeds and other foods. Evidence is emerging that certain dietary compounds may increase cancer cells' sensitivity to drugs and radiation.
Genistein, an isoflavone found in soy, has been the focus of a group of researchers at the Karmanos Cancer Institute at Wayne State University. Starting 10 years ago, Fazlul H. Sarkar, Ph.D., Professor of Pathology, began zeroing in on how genistein inhibits nuclear factor-kappa B, a protein molecule that has recently been implicated in making cancer cells resistant to treatment from drugs and radiation. In laboratory studies, Dr. Sarkar found that genistein along with chemotherapy promoted apoptosis in treated cells, compared to cells treated with genistein or chemotherapy alone.
Gilda Hillman, Ph.D., Associate Professor of Radiation Oncology at Karmanos, began work with Dr. Sarkar to test if genistein also enhanced the effects of radiation in killing prostate cancer cells. Supported by an AICR grant, Dr. Hillman found that genistein combined with radiation treatment inhibited cancer cell growth significantly more than radiation or genistein treatment alone.
Results on human breast and renal cancer cells were similar. Once Dr. Hillman found the optimal dose and schedule of combined genistein and radiation treatment, she studied the radiosensitization effects of genistein in mice with prostate cancer.
The study found that the combination of genistein and radiation not only inhibited the growth of the prostate tumors, but also extended the lives of the mice. But the researchers discovered that genistein, when given without radiation therapy, promoted metastasis from prostate tumors to the adjacent lymph nodes. "This increased metastasis was a big concern, because we were already running clinical trials using soy," Dr. Hillman notes. In the human trials, no adverse effects were seen.
An important difference between the clinical and laboratory studies was that the mice had been treated with a solution of pure genistein, while the people received capsules containing whole soy powder. That difference proved to be key. When Hillman switched the mice to dried powder of whole soy, she found whole soy just as effective as genistein in radiosensitizing prostate tumors. Also, whole soy given without radiation did not increase metastasis to the lymph nodes.
Clinicians working with cancer patients at Karmanos have teamed up with Drs. Sarkar and Hillman to conduct three studies using soy along with conventional treatment. In two clinical trials, patients with breast or pancreatic cancer ingested a soy capsule in addition to their prescribed chemotherapy treatments.
The third trial is testing the effects of radiation treatment in patients with prostate cancer who also consume the soy extract capsules. Data about the antitumor effect of the combined treatment will be compared with historical data from similar patients, with results expected about a year from now.
In addition to genistein, researchers are investigating the sensitizing characteristics of other dietary agents. Curcumin, a phytochemical found in turmeric; indole-3-carbinol, an antioxidant found in cruciferous vegetables; EGCG, a flavonoid found in green tea; and resveratrol, a compound found in grape seeds and red grape skins, are among the substances shown to enhance the antitumor activity of various chemotherapeutic drugs. Research combining these dietary compounds with chemotherapeutic agents shows increased apoptosis and decreased proliferation in tumor cells from colorectal, liver and ovarian cancers.
In laboratory studies, genistein, curcumin, gamma-tocotrienol - a vitamin E component - and PABA (para-aminobenzoic acid), are among the dietary agents shown to sensitize cancer cells to radiation treatment. This enhanced radiosensitivity has been shown in prostate, cervical, esophageal, breast and melanoma cancer cells.
Dr. Hillman cautions that use of dietary agents is an adjunct to conventional therapy, not a substitute. "It's important for the lay public and for cancer patients to understand that nutrition alone cannot cure cancer," she notes. "Nutrition is very important but not sufficient to cure someone who has cancer."
"I think this is the beginning of something new, and now [the research] has to be proven by clinical trials," said Dr. Sarkar.All active news articles