To Screen and Identify Potential Herbal Medicines That Can Enhance the Effect of Radiotherapy by Inhibiting DNA Repair Machinery

Radiotherapy results in the production of a variety of ionizing radiation-induced lesions in DNA, and unrepaired DNA damage can lead to tumor cell death via apoptosis, autophagy, or senescence. Combining irradiation with drugs that can inhibit DNA repair is a concept to improve radiotherapy. Several preclinical and clinical trials have indicated that some herbal medicines possess great advantages to improve radio sensitivity in combining with irradiation and chemotherapeutic agents, suggesting that these herbal medicines may play roles in inhibition of DNA repair. However, experimentally, the sequence-independent nature of radiation-induced damage makes it difficult to study DNA repair in vivo. Therefore, their molecular mechanics are still largely unknown. In this project, we will first use a yeast model to screen herbal medicines that can enhance radio sensitivity by inhibiting DNA repair machinery. Second, we will use an inducible HO endonuclease system where we can induce double-strand break (DSB) at specific site to study the kinetics of DNA repair and activation of the DNA damage checkpoint following herbal medicines treatment in yeast and mammalian cells. Third, we will generate a genome-wide association study of herbal medicines on modulating DNA repair machinery. In this system, we are able to identify gene targets and molecular pathways of selected herbal medicines. Only by elucidating the molecular mechanisms of how herbal medicines influence DNA repair, will we be able to discover new combinations of drugs to improve radiotherapy.

Project ID:PC10401-0400
External Project ID:NSC102-2320-B182-012-MY3