Abstract：
: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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Basu HS,Thompson TA,Church DR,Clower CC,Mehraein-Ghomi F,Amlong CA,Martin CT,Woster PM,Lindstrom MJ,Wilding Gdoi
10.1158/0008-5472.CAN-08-2472subject
Has Abstractpub_date
2009-10-01 00:00:00pages
7689-95issue
19eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-08-2472journal_volume
69pub_type
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