Polyamine depletion induces G(1 )and S phase arrest in human retinoblastoma Y79 cells

BACKGROUND: Polyamines and ornithine decarboxylase (ODC) are essential for cell proliferation. DL-α-difluoromethylornithine (DFMO), a synthetic inhibitor of ODC, induces G(1 )arrest through dephosphorylation of retinoblastoma protein (pRb). The effect of DFMO on cell growth of pRb deficient cells is not known. We examined the effects of DFMO on pRb deficient human retinoblastoma Y79 cell proliferation and its molecular mechanism. METHODS: Using cultured Y79 cells, the effects of DFMO were studied by using polyamine analysis, western blot, gel shift, FACS and promoter analysis. RESULTS: DFMO suppressed the proliferation of Y79 cells, which accumulated in the G1 and S phase. DFMO induced p27/Kip1 protein expression, p107 dephosphorylation and accumulation of p107/E2F-4 complex in Y79 cells. CONCLUSION: These results indicate that p107 dephosphorylation and accumulation of p107/E2F-4 complex is involved in G(1 )and S phase arrest of DFMO treated Y79 cells.