NKH477 INHIBITS PROLIFERATION AND INDUCES APOPTOSIS IN A PANEL OF CANCER CELL LINES

Background and Objectives: The anti-proliferative effects of cAMP in cancer cells may be regulated by the adenylyl-cyclase-V isoform. As Colforsin Daropate (NKH477) is more selective for this isoform, we hypothesized that this water soluble compound may promise utility as an oral anti-tumour agent. Materials and Methods: Using separate cancer cell lines (MCF7, HT29, A431, WiDr, RKO, A375, H630, Du145, SW480 and SW620), we studied the effects of NKH477 on cell proliferation, cell viability and apoptosis. Results: NKH477 induced >70% inhibition of proliferation in all cancer cell lines tested. NKH477 induced a dose-dependent apoptosis causing G1 arrest and priming cells to die. Conclusions: NKH477 treatment on the tested cell lines inhibited proliferation and induced apoptosis. Thus, NKH477 shows early promise as an oral anti-cancer agent.