The fact that
tumors require
polyamines for growth has been demonstrated in vitro and in vivo and widely reported. This finding led to the use of
polyamine biosynthetic
enzymes as targets for
antitumor drug design. Highly efficient in vitro selective inhibitors of
ornithine decarboxylase such as DFMO do not produce important antitumoral effects in vivo, due to the ability of
tumor cells to uptake extracellular
polyamines. A new strategy was developed, combining a systematic blockade of all endogenous and exogenous sources of
polyamines in vivo. Sources of exogenous
polyamines were eliminated by administration of a
polyamine-free diet to the animals and decontamination of their gastrointestinal tract. Important antitumoral effects were obtained with this
polyamine deprivation and are presented with two experimental models of
tumors (
Lewis lung carcinoma, Mat Lylu prostatic
carcinoma).
Biological parameters, modified in cases of
cancer, were restored to normal values in treated animals: blood counts and NK cytotoxic activity. Number of
metastases was significantly reduced. Given that in man
cancer treatment remains unsatisfactory due to incomplete cell kill, development of resistance to treatment and secondary effects of
chemotherapy, we chose to investigate the potential interest of
polyamine deprivation in this field. By combining clinically applied cytotoxic drugs with
polyamine deprivation, we observed an improvement of their antitumoral efficiency: a considerable retardation of
tumor growth paired with a marked increase in life-span of the treated animals. Our observations confirm that
polyamines absorbed from exogenous sources, mainly food and gastrointestinal tract, play an important role in
tumor growth control. Furthermore, the study shows that
polyamine deprivation represents an important potential therapeutic tool in improved management of
cancer treatment.