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01-11-2003 | Original Article

Induction of the PAOh1/SMO polyamine oxidase by polyamine analogues in human lung carcinoma cells

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2003

Abstract

Purpose

The induction of polyamine catabolism has been directly associated with the cytotoxic response of various tumor types to the antitumor polyamine analogues. Initially, human polyamine catabolism was assumed to be under the control of a rate-limiting spermidine/spermine N¹-acetyltransferase (SSAT) that provides substrate for an acetylpolyamine oxidase (PAO). We have recently cloned a new polyamine analogue-inducible human polyamine oxidase (PAOh1/SMO) that efficiently uses spermine as a substrate. The induction of PAOh1/SMO in response to multiple polyamine analogues was examined in representative lung tumor cell lines.

Methods

Representatives of three different classes of antitumor polyamine analogues were examined for their ability to induce PAOh1/SMO.

Results

The human adenocarcinoma line, NCI A549 was found to be the most responsive line with respect to induction of PAOh1/SMO in response to analogue exposure. Similar to previous observations with SSAT expression, PAOh1/SMO induction was found to occur primarily in non-small-cell lung cancers cell lines. Using a series of polyamine analogues, it was found that the most potent inducers of PAOh1/SMO possessed multiple three-carbon linkers between nitrogens, as typified by N¹,N¹¹-bis(ethyl)norspermine.

Conclusions

Since PAOh1/SMO is an analogue-inducible enzyme that produces H₂O₂ as a metabolic product, it may play a significant role in determining the sensitivity of various human tumors to specific polyamine analogues.

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Title: Induction of the PAOh1/SMO polyamine oxidase by polyamine analogues in human lung carcinoma cells
Publication date: 01-11-2003
Published in: Cancer Chemotherapy and Pharmacology / Issue 5/2003
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-003-0662-4

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Abstract

Purpose

Methods

Results

Conclusions

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