A small molecule polyamine oxidase inhibitor blocks androgen-induced oxidative stress and delays prostate cancer progression in the transgenic adenocarcinoma of the mouse prostate model
| Autor: | Corey A. Amlong, Mary J. Lindstrom, Hirak S. Basu, Dawn R. Church, Cynthia C. Clower, Patrick M. Woster, George Wilding, Todd A. Thompson, Farideh Mehraein-Ghomi, Christopher T. Martin |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty medicine.drug_class Spermine Mice Transgenic Biology Adenocarcinoma Article chemistry.chemical_compound Prostate cancer Mice Prostate Acetyltransferases Internal medicine Cell Line Tumor medicine Putrescine Animals Humans Enzyme Inhibitors RNA Small Interfering Oxidoreductases Acting on CH-NH Group Donors Prostatic Neoplasms Androgen medicine.disease Spermidine Disease Models Animal Oxidative Stress Endocrinology medicine.anatomical_structure Oncology chemistry Tumor progression Cancer research Androgens Disease Progression Polyamine Reactive Oxygen Species Polyamine oxidase |
| Zdroj: | Cancer research. 69(19) |
| ISSN: | 1538-7445 |
| Popis: | High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiologic factor in prostate cancer (CaP) occurrence, recurrence, and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells, as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data show that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays CaP progression. [Cancer Res 2009;69(19):7689–95] |
| Databáze: | OpenAIRE |
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