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STUDY: S-adenosylmethionine decarboxylase activity and utilization of exogenous putrescine are enhanced in colon cancer cells stimulated to grow by EGF.
JOURNAL: Z Gastroenterol 1998 Nov;36(11):947-54
AUTHORS: Milovic V, Turhanowa L, Fares FA, Lerner A, Caspary WF, Stein J
ABSTRACT: Polyamines spermidine and spermine and their precursor putrescine are necessary for cell growth. Polyamine content is high in rapidly growing malignant cells, due to enhanced putrescine synthesis by ornithine decarboxylase (ODC), and increased uptake. In contrast to other cells of the body, colon cancer cells are exposed to high putrescine concentrations from the lumen. AIMS: To investigate the utilization of luminal putrescine in colon cancer, we studied the effect of a potent mitogen, epidermal growth factor (EGF), on the activity of the enzyme responsible for putrescine conversion, S-adenosylmethionine decarboxylase (SAMDC), in Caco-2 cells.RESULTS: ODC and SAMDC activity and putrescine uptake were strongly stimulated by EGF. Both synthesized and absorbed putrescine was rapidly converted to spermidine and spermine after EGF. Conversion pattern was identical in the cells stimulated with EGF only and EGF plus exogenous putrescine, indicating that, if stimulated to proliferate, colon cancer cells utilize the entire available putrescine pool. SAMDC inhibitor, methylglyoxal-bis-guanylhydrazone, induced growth arrest which was not reversed by exogenous putrescine, but only by high concentrations of spermidine. CONCLUSION: Enhanced proliferation in colon cancer cells is associated with increased SAMDC activity and rapid conversion of putrescine to spermidine and spermine. SAMDC might be a preferable target for therapeutic attempts to impair growth by reducing intracellular polyamine pools in colon cancer.
COMMENTARY: I've talked about the polyamine producing enzyme ornithene decarboxylase (ODC) in the past. Polyamines, naturally occurring amines, include putrescine, spermidine, cadaverine and spermine. Polyamines are ubiquitously distributed throughout our cells. Cell proliferation and differentiation appear to require their biosynthesis; furthermore, their generation is tightly regulated. Cancer cells, especially those known to be steroid or insulin sensitive, are voracious consumers of polyamines. The parent substance from which putrescine (and hence, the other polyamines) is produced is the amine acid ornithine in a reaction which is catalyzed by ornithine decarboxylase (ODC).
S-Adenosylmethionine Decarboxylase (SAMDC) is a critical regulatory enzyme in the polyamine synthetic pathway. SAMDC catalyzes the removal of the carboxylate group from S-adenosylmethionine (SAMe) to form S-adenosyl-5'-3-methylthiopropylamine. This acts as the n-propylamine donor to synthesize spermidine and spermine from putrescine.Thus the enzyme SAMDC converts SAMe into the polyamines spermidine and spermine which then can act as growth stimulators for cancer cells. Of interest is the fact that this process is stimulated by the hormone EGF (Epidermal Growth Factor) which often is simualtaneously upregulated in many hormonally sensitve cancers such as those of the breast. One additional down-side of being type A or AB with regard to cancer risk is the fact that the type A antigen also fits the receptor for epidermal growth factor.So, if you are type A, should you take SAMe? I recommend against it, or if you do make sure you drink lots of green tea: Green tea polyphenols inhibit ODC which limits the amount of putrescine available for SAMDC to convert to spermine.