Role of Polyamine Oxidase (PAOH1/SMO) in Human Breast Cancer
Abstract
Bis(ethyl)norspermine (BENSpm) is a spermine analogue that has shown antitumor activity in multiple human tumor models. This project evaluates the ability of BENSpm to induce the polyamine catabolic enzyme spermine oxidase, SMO(PAOhl), in human breast cancer cell lines and examined the role of its induction in the overall response of breast cancer cell lines to BENSprn treatment. BENSpm differentially induced SMO(PAOhl) mRNA and activity in several breast cancer cell lines. The greatest induction was seen in MDA-MB-23l cells, which exhibited a time- and dose- dependent induction of SMO(PAOhl) mRNA and activity with BENSpm treatment. Although SMO(PAOhl) was not induced in MCF-% and T47D cells, BENSpm exposure inhibited cell growth, decreased intracellular polyamine levels, decreased ODC activity, and induced SSAT activity in all of the cell lines examined. Inhibition of SNO(PAOhl) activity with the polyamine oxidase inhibitor MDL 72,527 reduced the sensitivity of MDA-MB-23l and Hs578t cells to BENSpm but had no effect on the response of MCF-7 and T47D cells to exposure to BENSpm. These results indicate that the induction of SNO(PAohl) may play a role in the response of specific breast cancer cell lines to BENSpm treatment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA435245
Entities
People
- Allison M. Pledgie
Organizations
- Johns Hopkins University