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Polyamine-mediated cell migration and growth: Structural requirements for diamine analogues to substitute for putrescine

, : Polyamine-mediated cell migration and growth: Structural requirements for diamine analogues to substitute for putrescine. Cellular Pharmacology 2(3): 109-113

Studies from our laboratory have shown, utilizing the small intestinal epithelial crypt cell line IEC-6, that the polyamines spermidine and spermine, and their precursor putrescine are essential to both the early process of cell migration and the later one of cell division. In that model, inhibition of ornithine decarboxylase, a rate-limiting enzyme of polyamine biosynthesis with alpha-difluoromethylornithine (DFMO) almost entirely prevented migration and growth. Although there is a great deal of evidence that polyamines play a role in gastrointestinal mucosal growth, the actions of polyamines at the molecular level remain to be elucidated. Thus, in the current study we have examined the structure-function characteristics of analogues to putrescine (diamines) on IEC-6 cell migration and growth. All diamine analogues (except diaminopropane, 3 carbons) were able to inhibit the transport of labeled putrescine into the cells. Treatment of the cells with DFMO for 4 days reduced cell migration 70%. Migration could be restored to normal by concomitant treatment with putrescine (4 carbons) however, none of the analogues with chain lengths varying from 3-10 carbons supported cell migration. In other experiments, DFMO dramatically attenuated cell growth (60%) which was restored by concurrent addition of putrescine. Unlike the migration experiments, addition of the putrescine analogues diaminopropane (3 carbons) and cadaverine (5 carbons) to the DFMO- treated cells resulted in a significant restoration of cell growth. These experiments indicate that although the analogues were recognized by the putrescine carrier, only analogues with less than 5 carbons were able to exert well characterized putrescine biological effects.


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