Structural requirements of analogues of polyamines for migration and growth of IEC-6 cells

Healing of gastrointestinal mucosal lesions occurs through two processes: an early one involving cell migration and a later one in which cell division replaces lost cells. Both processes require the presence of polyamines, but the mechanism of action of these compounds is unknown. In the present study, we examined the ability of analogues of spermidine and spermine to support migration and growth of IEC-6 cells that have been grown in alpha-difluoromethylornithine to inhibit polyamines. All analogues of spermidine with the general formula x-3 (referring to the numbers of carbon atoms on either side of the central nitrogen), where x = 2-12, competed with spermidine for entry into the cells. However, in addition to spermidine (x = 4), only compounds for which x = 2, 3, or 6 supported migration and only those for which x = 2 or 7 supported growth. Spermine analogues 3-x-3, for which x = 3, 6, 9, or 12, competed for entry into the cells, but only compounds for which x = 3 or 6 supported migration and only the compound for which x = 3, in addition to spermine (x = 4), supported growth. In addition, analogues 2-3-2, 3-2-3, and 2-(3)2, a branched compound, supported both migration and growth but entered the cell via a mechanism different than that for spermidine and spermine. These data define some of the specific structural requirements for polyamines to produce their physiological effects.