Disruption of Brca2-Rad51 Complex in Breast Cancer Cells: Therapeutic Implications

BRCA2-Rad51 interaction is required for the Rad51-related DNA repair pathway. Thus, inhibition of their interaction is expected to sensitize tumor cells to certain DNA damaging agents. A panel of 14080 natural compounds from the Chinese National Center for Drug Screening has been partially screened using a yeast two-hybrid system utilizing specific Rad51/BRCA2 constructs. Growth of the Rad51/BRCA2 yeast strain in different media lead us to the selection of 20 candidate inhibitors for BRAC2-Rad51 interaction. We are actually testing if these compounds sensitize breast cancer cell lines to cisplatin. One of the compounds at the concentrations attainable increases the toxicity of cisplatin in a BRCA1 deficient breast cancer cell line. The original document contains color images.