Soy Used to Protect Normal Cells While Sensitizing Cancer Cells to Radiation
Division of Cancer Treatment and DiagnosisAlthough radiation therapy can be a powerful treatment for lung cancer, normal lung tissue is very sensitive to radiation-induced damage. Inflammation of the lungs and the formation of scar tissue, which can occur weeks to months after treatment, pose particular risks for patients. These side effects limit the amount of radiation that can be aimed at a lung tumor, potentially decreasing the effectiveness of the therapy.
Under a grant from NCI*, Gilda Hillman, Ph.D., professor of radiation oncology at Wayne State University and the Barbara Ann Karmanos Cancer Institute in Detroit, Michigan, is studying whether natural soy isoflavones can both protect normal lung cells from radiation damage and increase the toxic effects of radiation on lung cancer cells.
Her research team first asked these questions 12 years ago, in collaboration with a colleague at Wayne State, Fazlul Sarkar, Ph.D., whose laboratory had been testing natural compounds to sensitize cancer cells to chemotherapy drugs. At that time, Dr. Hillman’s research focused on combining radiation therapy with immunotherapy in several mouse models of cancer. Dr. Sarkar suggested that they try combining their areas of research to test soy isoflavones with radiation in cancer cells and in her mouse cancer models. “I tried it, and it worked!” recounted Dr. Hillman.
Since 2000, her laboratory has painstakingly teased out the details of the molecular mechanisms behind the two complementary effects observed by combining soy isoflavones and radiation: increased cancer cell death and decreased damage to normal cells.
To increase death of cancer cells, the isoflavones found in soy – including genistein, daidzein, and glycitein – seem to interfere with lung cancer cells’ ability to repair the DNA damage incurred from radiation exposure, Dr. Hillman said. In their experiments, when she and her colleagues irradiated cancer cells without adding soy isoflavones, the cells rapidly activated repair pathways that fixed radiation-induced DNA damage, allowing some of the cells to live and continue dividing.
When the researchers added soy isoflavones to radiation exposure, these repair pathways were inhibited, leading to increased cancer cell death, Dr. Hillman explained. This suggests that blocking these pathways with soy isoflavones should be effective in cancer cells without causing damage to normal cells.
In fact, soy isoflavones appear to have a protective effect in normal lung tissue. In recent mouse studies from Dr. Hillman’s laboratory, soy isoflavones given during and after radiation therapy reduced bleeding, inflammation, and scarring in normal lung tissue in mice treated with radiation**. At the same time, “soy increased the killing of tumor cells induced by radiation, thus playing a differential role in tumor versus normal cells,” she said.
Dr. Hillman and her colleagues are currently planning a trial for lung cancer patients, looking at the combination of radiation therapy, chemotherapy with the drugs cisplatin and etoposide or pemetrexed, and soy. Patients will continue to take soy for 6 months after treatment, “since studies in our lab have shown that the effects of soy are better if you continue it after the end of radiation therapy,” explained Dr. Hillman. The researchers hope to start the trial after securing a reliable, tested supply of soy isoflavone tablets that meet their standards for proof of safety.
NCI Program Director Dan Xi, Ph.D. commented, “This project addresses an established research area of special interest for complementary approaches that enhance the effects of conventional cancer therapies. It is our hope that this study, if successful, could ultimately lead to a better therapeutic strategy for non-small cell lung cancer care.”
* Grant number: 1R21CA155518-01A1
** Hillman G.G., Singh-Gupta V., Runyan L., Yunker C.K., Rakowski J.T., Sarkar F.H., Miller S., Gadgeel S.M., Sethi S., Joiner M.C., & Konski A.A. (2011). Soy isoflavones radiosensitize lung cancer while mitigating normal tissue injury. Radiotherapy and Oncology, 101(2),329-36.