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

Autor:	Devereux, Wendy, Wang, Yanlin, Stewart, Tracy Murray, Hacker, Amy, Smith, Renee, Frydman, Benjamin, Valasinas, Aldonia L., Reddy, Venodhar K., Marton, Laurence J., Ward, Tracey D., Woster, Patrick M., Casero, Robert A.
Předmět:	LUNG cancer CANCER cells REACTIVE oxygen species POLYAMINES ACETYLTRANSFERASES AMINES BIOCHEMISTRY CELL lines COMPARATIVE studies DOSE-effect relationship in pharmacology GENES IMMUNOBLOTTING LUNG tumors PHENOMENOLOGY RESEARCH methodology MEDICAL cooperation MOLECULAR structure NUCLEOTIDE separation OXIDOREDUCTASES RESEARCH RESEARCH funding RNA TIME EVALUATION research SMALL cell carcinoma
Zdroj:	Cancer Chemotherapy & Pharmacology; Nov2003, Vol. 52 Issue 5, p383-390, 8p
Abstrakt:	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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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