Cell Pathways CP461 demonstrates multiple anti-cancer ...( i-proliferative effect. At AACR Cell P...)

i-proliferative effect. At AACR, Cell Pathways scientists and collaborators at Columbia University College of Physicians and Surgeons report that multiple cancer cell lines treated with CP461 become blocked in the cell cycle at prometaphase, preventing their subsequent division and selectively forcing them to undergo apoptosis. Moreover, in the research presented, CP461 did not trigger apoptosis in normal human foreskin fibroblasts or normal human mammary epithelial cells (HMEC).

Studies showed that CP461 does not directly bind to tubulin or affect its polymerization/ depolymerization properties like some types of conventional chemotherapeutic agents, but instead disrupts microtubule organization and proper spindle formation cellular structures essential to the process of cell division, said W. Joseph Thompson, Ph.D., Cell Pathways vice president, research and discovery. This prevents the chromosomes from properly aligning and blocks mitosis. He noted that the effects of CP461 on chromosome alignment and spindle formation occur at lower concentrations for cancerous over normal cells in these studies.

Target Validation of PDE5 Control of Apoptosis and Cell Proliferation

Prior studies have demonstrated the importance of cGMP phosphodiesterases as targets for Cell Pathways SAANDs compounds. New research directed toward target validation presented at AACR used antisense oligonucleotides to create cells in culture with very low PDE5. PDE5 may act as an important modulator of cell cycle progression, notably during the G2/M phase of the cell cycle leading to cell division. Cell Pathways researchers and collaborators at the University of South Alabama College of Medicine, demonstrated a positive correlation between PDE5 suppression, increased cGMP content and prolonged doubling times in human colon carcinoma cells stably transfected with the PDE5 antisense.

In addition to showing much higher rates of apoptosis, the antisense-transfect
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Contact: Joan Kureczka
Jkureczka@aol.com
415-821-2413
Kureczka/Martin Associates
8-Apr-2002

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