Disruption of Brca2-Rad51 Complex in Breast Cancer Cells: Therapeutic Implications
Annual rept. 1 Sep 2003-31 Aug 2005
SIR MORTIMER B DAVIS JEWISH GENERAL HOSPITAL MONTREAL (QUEBEC)
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BRCA2-Rad5l interaction is required for the Rad5l-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 Rad5lBRCA2 constructs. Growth of the Rad5lBRCA2 yeast strain in different media lead us to the selection of 20 candidate inhibitors for BRAC2-Rad5l interaction. Three of these compounds present minimal toxicity to the yeast strains respect to their specific inhibitory activity and thus are the first candidates to be tested for their ability to sensitize breast cancer cells to cisplatin.
- Anatomy and Physiology
- Medicine and Medical Research