Pharmacological and dietary agents for colorectal cancer chemoprevention: Effects on polyamine metabolism (Review)

Abstract

Abstract. Chemoprevention is the long-term use of different chemical agents, both synthetic and natural, to prevent or delay the onset of disease. Since colorectal cancer has a significant environmental component, it is an ideal disease in which to evaluate the potential benefits of chemopreventive agents. The polyamines, spermine, spermidine and putrescine have been involved in almost all the steps of colorectal tumorigenesis. Consequently, polyamine biosynthesis and catabolism can be considered as promising targets for cancer chemoprevention. A variety of drug formulations have been tested for their efficacy in affecting polyamines in a strategy of colorectal cancer prevention. Different molecules, such as biosynthesis inhibitors and catabolism inducers, have been proposed alone or in combination with other drugs proved to diminish the colorectal cancer risk. Interestingly, also diet can play a role in cancer prevention by affecting polyamines. Several dietary components, such as probiotics or flavonoids, have been shown to affect the polyamine metabolic pathway in colorectal neoplastic tissue. On the other hand, the polyamines ingested with diet might contrast the above cited effects shown by both drugs and nutritional factors. It is, therefore, fundamental to acquire more data also on these aspects in view of an innovative approach to colorectal oncology. This review summarizes data on the role of polyamine metabolism in neoplastic transformation of colorectal mucosa and as possible target for colorectal cancer chemoprevention. Attention will be focused on the influence of drugs and nutritional factors on polyamine metabolism, as well as the role played by dietary polyamines.

Inhibitory effect of vitamin K1 on growth and polyamine biosynthesis of human gastric and colon carcinoma cell lines

“…Data from the present study are in agreement with published studies performed using other nutritional components such as flavonoids, polyphenols and probiotics that have demonstrated how these factors are able to reduce the polyamine biosynthesis in different cancer cells, including the GI ones (38).…”

Intracellular spermine blocks TRPC4 channel via electrostatic interaction with C-terminal negative amino acids

“…Thus, in specific cancer cell, it may seek biological pathways that downregulate TRPC4 and TRPC5 channels. Interestingly, many of cancer cells and hyperproliferative diseases show high concentration of intracellular polyamines [20,40]. If this high concentration of polyamines are defense mechanism of cancer cells, antipolyamine agents such as 2-difluoromethylornithine (DFMO)-an ornithine decarboxylase (ODC) inhibitor-can be used as anticancer therapeutics for cancer cells with high TRPC4/5 expression profile, e.g., RCC.…”

Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications

“…ODC is a wellknown mediator of cancer risk across various types of cancer, including gastric and colorectal cancers (7)(8)(9)(10)(11). Importantly, chronic inflammation contributes to the process of carcinogenesis and we now implicate ODC as having a role in the establishment of chronic inflammation by tempering the M1 macrophage response to bacterial pathogens.…”

“…ODC uses the substrate, L-ornithine, to produce putrescine via a decarboxylation reaction (2,6). Given its essential and central role in regulating polyamine metabolism within cells, ODC has been highly studied and implicated in several malignancies, including breast, colorectal, and gastric cancer (7)(8)(9)(10)(11). However, most of the studies related to ODC have been focused on its role in epithelial cell function, leaving many questions surrounding the role of ODC in immune cells unanswered.…”