Metabolism and function of polyamines in cancer progression.

ABSTRACT

Polyamines are essential for the proliferation, differentiation, and development of eukaryotes. They include spermine, spermidine, and the diamine precursor putrescine, and are low-molecular-weight, organic polycations with more than two amino groups. Their intracellular concentrations are strictly maintained within a specific physiological range through several regulatory mechanisms in normal cells. In contrast, polyamine metabolism is dysregulated in many neoplastic states, including cancer. In various types of cancer, polyamine levels are elevated, and crosstalk occurs between polyamine metabolism and oncogenic pathways, such as mTOR and RAS pathways. Thus, polyamines might have potential as therapeutic targets in the prevention and treatment of cancer. The molecular mechanisms linking polyamine metabolism to carcinogenesis must be unraveled to develop novel inhibitors of polyamine metabolism. This overview describes the nature of polyamines, their association with carcinogenesis, the development of polyamine inhibitors and their potential, and the findings of clinical trials.