A selective novel radiosensitizer for radiotherapy of cancer

Radiotherapy is a standard treatment for the solid tumors in cancer patients, which is often restricted by its high dose related toxicity to normal tissue and development of therapeutic resistance in cancer cells. We observed a preferential radiosensitizing effects of a small molecule, silibinin in invitro and pre-clinical tumor xenograft models of prostate cancer. Results are encouraging and reveal that the desired tumor growth inhibition can be achieved at lower doses of radiation treatment when it is combined with silibinin given orally. Various parameters including cell cycle, DNA damage and apoptosis were measured. Importantly, silibinin exhibited preferential radiosensitization of cancer cells and protected normal cells and tissues including various hematopoietic parameters from radiation-induced toxicities. Radiosensitization mechanism involved inhibition of nuclear translocation of EGFR and DNA-PK, indicating its effect on DNA repair signaling. The silibinin concentration used in this study can be physiologically achievable in patients which underlines the translational significance of this study for the radiotherapy for prostate cancer patients. (author)