Polyamines and colon cancer.
In colon cancer, the activities of polyamine-synthesizing enzymes and polyamine content are increased 3-4-fold over that found in the equivalent normal colonic mucosa, and polyamines have even been attributed as markers of neoplastic proliferation in the colon. Furthermore, and in contrast with all other cell systems in the body, normal and neoplastic cells in the colon are exposed to high concentrations of putrescine from the lumen, synthesized by colonic microflora. While such a high polyamine supply may be of benefit in non-neoplastic colonic mucosal growth, the role of luminal polyamines in colon cancer is a clear concern. Luminal polyamines are readily taken up by neoplastic colonocytes, they are utilized in full to support neoplastic growth, and their uptake is strongly up-regulated by the mitogens known to play an important role in colonic carcinogenesis. Inhibition of polyamine synthesis and their uptake, impaired utilization of exogenous polyamines, and enhanced catabolism of polyamines in neoplastic colonocytes are therefore logical approaches in the chemoprevention of colorectal cancer.
Milovic
V
V
2nd Department of Medicine and Department of General Pharmacology, J.W. Goethe University, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. vladen.milovic@med.uni-tuebingen.de
Turchanowa
L
L
D000970:Antineoplastic Agents / Q000494:pharmacology; D015317:Biogenic Polyamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014408:Biomarkers, Tumor; D003110:Colonic Neoplasms / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D011700:Putrescine / Q000037:antagonists & inhibitors / Q000378:metabolism
D000970:Antineoplastic Agents; D015317:Biogenic Polyamines; D014408:Biomarkers, Tumor; D011700:Putrescine