title: Decreased sensitivity to aspirin is associated with altered polyamine metabolism in human prostate cancer cells.
abstract: Aspirin is a well-known analgesic, anti-inflammatory and antipyretic drug and is recognised as a chemopreventative agent in cardiovascular disease and, more recently, in colorectal cancer. Although several studies indicate that aspirin is capable of reducing the risk of developing cancers, there is a lack of convincing evidence that aspirin can prevent prostate cancer in man. In this study, aspirin was shown to be an effective inhibitor of the growth of human prostate cancer cells. In order to investigate the link between polyamine catabolism and the effects of aspirin we used a "Tet off" system that induced the activity of spermidine/spermine N (1)-acetyltransferase (SSAT) in human prostate cancer cells (LNCap). Treatment with aspirin was found to decrease induced SSAT activity in these cells. A negative correlation was observed between increased polyamine catabolism via increased SSAT activity and the sensitivity to aspirin. In the presence of increased SSAT activity high amounts of N (1)-acetylspermidine and putrescine were observed. These cells were also found to grow more slowly than the non-induced cells. The results indicate that SSAT and its related polyamine metabolism may play a key role in sensitivity of cancer cells to aspirin and possibly other NSAIDs and this may have implications for the development of novel chemopreventative agents.
authors.affiliation: Division of Applied Medicine, School of Medicine and Dentistry and School of Medical Sciences, University of Aberdeen, Aberdeen, UK.|Cancer Research Centre, Western General Hospital, University of Edinburgh, Edinburgh, UK.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Applied Medicine, School of Medicine and Dentistry and School of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Cameron
authors.affiliation: Division of Applied Medicine, School of Medicine and Dentistry and School of Medical Sciences, University of Aberdeen, Aberdeen, UK. h.m.wallace@abdn.ac.uk.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Wallace
mesh_terms: D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011700:Putrescine / Q000378:metabolism*; D013095:Spermidine / Q000378:metabolism*; D013096:Spermine / Q000378:metabolism*; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D016588:Anticarcinogenic Agents; D001241:Aspirin; D011700:Putrescine; D013095:Spermidine; D013096:Spermine; D000099228:Diamine N-Acetyltransferase
keywords: Polyamines; Prostate cancer; SSAT