Polyamine metabolism as target for cancer chemoprevention (review).

Molecular Basis of Inward Rectification: Structural Features of the Blocker Defined by Extended Polyamine Analogs

“…Mutagenesis has indicated residues involved in the blocking process, and recent structural studies demonstrate the nature of the permeation path of Kir channels, within which the polyamines must bind (Nishida and MacKinnon, 2002;Kuo et al, 2003;Pegan et al, 2005). Further information may be obtained by examining the blocking abilities of a large collection of polyamine analogs that have been developed primarily in efforts to find anticancer agents (Seiler et al, 1998). We demonstrated previously that only the polyamines conferred strong rectification, whereas other bulkier, dipolar or nonlinear molecules (e.g., GABA, creatinine, lysine) fail to block these channels (Lopatin et al, 1994).…”

Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane‐induced colon carcinogenesis in male F344 rats

“…Polyamine levels in the surrounding colonic mucosa were also examined since polyamine is intimately involved in growth-related processes, including colon tumorigenesis, 21 and its metabolism is a target for cancer chemoprevention. 22 Colonic PGE 2 level and ␤-glucuronidase activity were also determined. Increased ␤-glucuronidase activity in either microflora or colonic mucosa plays an important…”

“…Polyamine levels in the surrounding colonic mucosa were also examined since polyamine is intimately involved in growth-related processes, including colon tumorigenesis, 21 and its metabolism is a target for cancer chemoprevention. 22 Colonic PGE 2 level and ␤-glucuronidase activity were also determined. Increased ␤-glucuronidase activity in either microflora or colonic mucosa plays an important Abbreviations: ACF, aberrant crypt foci; AOM, azoxymethane; CDNB, 1-chloro-2,4-dinitrobenzene; COX, cyclooxygenase; DCNB, 1,2-dichloro-4-nitrobenzene; DMH, 1,2-dimethylhydrazine; GST, glutathione S-transferase; HRP, horseradish peroxidase; LOX, lipoxygenase; MAb, monoclonal antibody; ODC, ornithine decarboxylase; PCNA, proliferating cell nuclear antigen; PG, prostaglandin; QR, quinone reductase; TNF, tumor necrosis factor.…”

Critical Factors Determining Dimerization of Human Antizyme Inhibitor

“…They also have been associated with human diseases and a variety of cancers (16 -26). Because the regulation of ODC and polyamine content is critical to cell proliferation (11), as well as in the origin and progression of neoplastic diseases (23, 24), ODC has been identified as an oncogenic enzyme, and the inhibitors of ODC and the polyamine pathway are important targets for therapeutic intervention in many cancers (6,11).…”

“…1,4,5). This enzyme catalyzes the pyridoxal 5-phosphate (PLP)-dependent decarboxylation of ornithine to putrescine, and it is the first and rate-limiting enzyme in polyamine biosynthesis (2,3,6,7). ODC and polyamines play important roles in a number of biological functions, including embryonic development, cell cycle, proliferation, differentiation, and apoptosis (8 -15).…”