Resveratrol Enhances the Sensitivity of Prostate Cancer to Radiation Therapy

Treatment of prostate cancer is significantly enhanced by combining radiation therapy with resveratrol, a bioactive compound found primarily in grape skins and red wine.

The toxicity of radiation therapy (XRT) for treatment of prostate cancer (PCA) and the relative resistance of PCA to ionizing radiation limit the effectiveness of this treatment method. Currently no safe and effective radiosensitizing agents have been found capable of enhancing the effectiveness of radiation treatment for PCA.

Investigators at the University of Missouri (Columbia, USA) evaluated the potential use of resveratrol as a radiosensitizing agent by studying the effectiveness of this approach on the radioresistant PCA cell line, PC-3. They reported in the June 2012 issue of the journal Cancer Science that the addition of resveratrol (RSV) to XRT (XRT/RSV) synergistically enhanced XRT-induced apoptosis and inhibition of PC-3 proliferation. The antiproliferative effect of XRT/RSV treatment correlated with increased expression of the p15, p21, and mutant p53 genes and decreased expression of cyclin B, cyclin D, and cdk2. In some cultures up to 97% of the tumor cells were killed, a much higher percentage than the number of cells killed by radiation treatment alone.

In a second paper, the investigators looked at the molecular basis for the increase in radiosensitivity induced by resveratrol. They reported in the July/August 2012 issue of the Journal of Andrology that the expression of two proteins, perforin and granzyme B was increased in PCA cells exposed to XRT/RSV treatment to a greater extent than was found in PCA cells treated with separately with RSV or XRT. Perforin and granzyme B, which are not usually found in tumor cells, are expressed primarily by activated lymphocytes (cytotoxic T cells, natural killer cells, and natural killer T cells) and function together to induce apoptosis of target cells.

"Other studies have noted that resveratrol made tumor cells more susceptible to chemotherapy, and we wanted to see if it had the same effect for radiation therapy," said senior author Dr. Michael Nicholl, assistant professor of surgical oncology at the University of Missouri. "We found that when exposed to the compound, the tumor cells were more susceptible to radiation treatment, but that the effect was greater than just treating with both compounds separately."

"It is critical that both proteins, perforin and granzyme B, are present in order to kill the tumor cells, and we found that the resveratrol helped to increase their activity in prostate tumor cells," said Dr. Nicholl. "Following the resveratrol-radiation treatment, we realized that we were able to kill many more tumor cells when compared with treating the tumor with radiation alone. It is important to note that this killed all types of prostate tumor cells, including aggressive tumor cells."

Related Links:
University of Missouri