Metabolism and function of polyamines in cancer progression.

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.

Serum deprivation increases the expression of low density lipoprotein receptor-related protein in primary cultured rat astrocytes.

The low density lipoprotein receptor (LDLR)-related protein (LRP) is a multifunctional receptor which mediates the endocytic uptake of several ligands implicated in Alzheimer's disease pathophysiology. Although LRP, as a member of the LDLR family, is likely to be regulated in response to various cellular stresses, this regulation has not been fully understood yet. In the present study we studied the regulation of LRP expression in primary cultured rat astrocytes in response to serum deprivation as a general cellular stress. A significant increase in LRP expression was detected after serum deprivation and this increase was blocked by treatment of U0126, an inhibitor of MAP kinase. This serum deprivation action was partially reversed by either serum or D-glucose supplementation, but further augmented by glutamine. This result contrasted with a finding that glutamine suppressed gadd153 protein induced by serum deprivation. Taken together, the present data suggest that serum deprivation induces dramatically LRP expression in astrocytes partly by MAPK signaling pathways and by signaling pathways apparently distinct from gadd153 induction.