The R-enantiomer of ketorolac reduces ovarian cancer tumor burden in vivo
Abstract
Rho-family GTPases, including Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42), are important modulators of cancer-relevant cell functions and are viewed as promising therapeutic targets. Based on high-throughput screening and cheminformatics we identified the R-enantiomer of an FDA-approved drug (ketorolac) as an inhibitor of Rac1 and Cdc42. The corresponding S-enantiomer is a non-steroidal anti-inflammatory drug (NSAID) with selective activity against cyclooxygenases. We reported previously that R-ketorolac, but not the S-enantiomer, inhibited Rac1 and Cdc42-dependent downstream signaling, growth factor stimulated actin cytoskeleton rearrangements, cell adhesion, migration and invasion in ovarian cancer cell lines and patient-derived tumor cells.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 07, 2021
- Source ID
- 10.1186/s12885-020-07716-1
Entities
People
- Angela Wandinger-ness
- Dayna R. Dominguez
- Kathryn J. Brayer
- Laurie G. Hudson
- Martha M. Grimes
- S. Ray Kenney
- Yuna Guo
Organizations
- National Cancer Institute
- National Center for Advancing Translational Sciences
- National Center for Research Resources
- National Institute of General Medical Sciences
- United States Department of Defense