Cell Cycle Target-based Therapy for Ovarian Cancer
Abstract
In many tumors, the actively dividing cells account for only a small proportion of the total, with the remainder of the cells being in a quiescent state or GO. Indeed, tumor cell population in GO ranges from 70-95% and the quiescent cell population of tumors poses a barrier to the success of many cancer therapies. Numerous studies demonstrate that non-steroidal anti-inflammatory drugs (NSAIDs) hold significant promise as anti-cancer therapeutics. We started identifying now the best of NSAIDs therapy for apoptosis induction of quiescent ovarian cancer cells. In this report we show that structurally unrelated NSAIDS induces apoptosis in quiescent ovarian cancer cells. Strong inducers of apoptosis included flufenamic acid, flurbiprofen, celebrex and finasteride, whereas treatment with ibuprofen in low levels of apoptosis. Additionally, the spectrum of NSAIDs obtained in this analysis differs from the spectrum of NSAIDs obtained by our group for induction of apoptosis in proliferative ovarian cancer cells. In vivo experiments corroborated our in vitro data. The treatment with NSAIDs, which act in the proliferative stage in combination with NSAIDS, which act in the quiescent stage, had a synergistic effect in reducing tumor formation compared with single drug treatment. Our results offer a multitude of novel entry points for drug development and will provide opportunities for a rational design of new combination treatment modalities for ovarian cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2008
- Accession Number
- ADA493717
Entities
People
- Luiz F. Zerbini
Organizations
- Beth Israel Deaconess Medical Center