Inhibition of cell growth in CaCO2 cells by the polyamine analogue N1,N12-bis(ethyl)spermine is preceded by a reduction in MYC oncoprotein levels.

Abstract:

:The polyamine analogue N1,N12bis(ethyl)spermine (BESpm) is a potent inhibitor of cell proliferation and is representative of a class of agents currently in clinical trials. Previous studies have demonstrated that BESpm treatment can produce a decrease in the mRNA levels of the protooncogene c-myc resulting from decreased transcription. Investigation into the mechanism of the antiproliferative effect of BESpm in the colon cancer cell line CaCO2 indicated that significant reduction in MYC protein, but not c-myc mRNA levels, preceded cytostasis. Specificity of the downregulation of MYC expression by BESpm treatment was demonstrated by comparison to effects on the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT) and the polyamine biosynthetic enzyme ornithine decarboxylase (ODC). SSAT activity rapidly increased while levels of ODC activity decreased after BESpm treatment. Measurement of intracellular polyamines demonstrated significant uptake of the analogue after 24 hours, which was concurrent with a reduction of spermine and spermidine levels. Thus, cellular uptake of BESpm mediated a reduction of polyamine levels that was associated with a decrease of MYC protein at the post-transcriptional level.

journal_name

J Cell Physiol

authors

Berchtold CM,Tamez P,Kensler TW,Casero RA Jr

doi

10.1002/(SICI)1097-4652(199803)174:3<380::AID-JCP1

subject

Has Abstract

pub_date

1998-03-01 00:00:00

pages

380-6

issue

3

eissn

0021-9541

issn

1097-4652

pii

10.1002/(SICI)1097-4652(199803)174:3<380::AID-JCP1

journal_volume

174

pub_type

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