Polyamines in normal and cancer cells.

Based on available evidence, it appears that polyamines are critical for proliferation of both normal and transformed cells. Although the requirement of polyamines for DNA replication and cell proliferation is established, the molecular events in which the polyamines are essential are yet unknown. Furthermore, transformed and cancer cells, possibly because of their higher proliferative rate, appear to be more dependent on polyamine metabolism than their normal counterparts. This has been shown by the in vivo response of tumor models and human tumor xenografts in nude mice to polyamine depletion by DFMO. Although there has been associated toxicity to the host, the inhibition of cell proliferation has been higher in the implanted tumors than in the host. DFMO, a specific irreversible inhibitor of ODC, has been used extensively in studies which have shed light on the role of polyamines in cell proliferation and differentiation. DFMO has shown interesting anti-tumor effect in a number of experimental tumor models. Currently, DFMO clinical trials are being completed, and it will be of interest to see whether this polyamine inhibitor, or other newer polyamine analogs and inhibitors, will find a place in the treatment of neoplastic disorders.