Development of polyamine analogs as cancer therapeutic agents

Abstract

Natural polyamines (putrescine, spermidine, and spermine) are aliphatic cations with multiple functions in cell growth and differentiation. Alterations in the polyamine structure provide a strategy to synthesize analogs that can interfere with the cellular functions of natural polyamines. Analogs of spermine are particularly effective in modifying the synthesis, catabolism, and uptake of natural polyamines. The increased requirement of natural polyamines in cancer cell growth makes it possible to utilize the polyamine pathway as a therapeutic target in cancer cells. Because polyamine functions extend from membrane phospholipid structure and signal transduction to DNA structure and conformational transitions, it is likely that the action of polyamine analogs also permeates to these sites of polyamine action. For the same reason, toxicity of polyamine analogs might be considerable. However, it is possible to design polyamine analogs that target a specific function of polyamines in cancer cells, thereby enhancing selectivity for inducing apoptosis of cancer cells. Alternatively, polyamine analogs may potentiate the action of other anticancer agents and become an effective tool in cancer chemotherapy. In either case, further research into the action of polyamine analogs will open up new opportunities in the fight against cancer.