Cell Pathways CP461 demonstrates multiple anti-cancer ...( ed cells with low PDE5 and high cGMP ex...)

ed cells with low PDE5 and high cGMP exhibited a progression time of up to 72 hours versus vector control cells, which progressed to G2/M phase within 24 hours, said Dr. Thompson. The antisense inhibition of PDE5 has revealed a novel role for this enzyme to regulate progression during the G2/M phase of the cell cycle. The altered progression during G2/M also appears to enhance the sensitivity of the cancer cells to triggering of the PKG-dependent apoptotic mechanism.

In related studies also being presented at AACR, Cell Pathways collaborators at Columbia University College of Physicians and Surgeons demonstrated cells transfected with constitutively active PKG decreased beta catenin and increased apoptosis in colon tumor cells. Alternatively, cells that stably expressed a dominant negative form of PKG (an inactive form of PKG that dominates over the normal molecule without toxicity to the cell) grew more rapidly and were more resistant to apoptosis induction by SAANDs such as Cell Pathways first-generation SAAND, exisulind (Aptosyn).

These intact cell data provide substantive in vitro evidence that our proposed mechanism of regulation by SAANDs cGMP PDE governing cGMP levels governing PKG -- operates in colon tumor cells, commented Dr. Thompson.

About Cell Pathways

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Contact: Joan Kureczka
Jkureczka@aol.com
415-821-2413
Kureczka/Martin Associates
8-Apr-2002

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