Morphological Evidence for an Apparent Lysosomotropic Activity by Unsaturated Putrescine Analogues

Department

Natural Sciences

Document Type

Article

Publication Source

Cancer Research

Publication Date

1990-03-15

Volume

50

Issue

6

First Page

1929

Last Page

1935

Abstract

Treatment of cultured LI210 cells with the putrescine analogue, 2,5-diamino-3-hexyne, at 0.5 dim resulted in the rapid (1–2 h) appearance of numerous cytoplasmic vacuoles which were highly visible by light microscopy. Ultrastructural examination revealed that the vacuoles contained numerous membrane vesicles and electron-dense structures resembling endosomal elements. Other cellular organelles were unaffected by the drug. The overall morphological effect by 2,5-diamino-3-hexyne was nearly identical to that produced in the same cells by the known lysosomotropic agent, chloroquine. Since the putrescine analogue, l,4-diamino-2-butyne at 1.2 dim, also produced comparable cytoplasmic vacuolation, and putrescine itself failed to do so at concentrations as high as 5 mM, it was concluded that the apparent lysosomotropic activity of the putrescine analogues was probably due to their weaker basicity related to the presence of an internal triple bond. Although it is uncertain whether the effect of the analogues on the endosomal system is related to the natural function of polyamines, the finding points out the previously unrecognized potential for certain polyamine analogues to act in this manner. © 1990, American Association for Cancer Research. All rights reserved.

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