Polyamine depletion therapy in prostate cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2000-12

AUTHORS

BH Devens, RS Weeks, Burns, CL Carlson, MK Brawer

ABSTRACT

The prostate gland has among the highest level of polyamines in the body and prostate carcinomas have even greater elevated polyamine levels. These ubiquitous molecules synthesized by prostate epithelium are involved in many biochemical processes including cellular proliferation, cell cycle regulation, and protein synthesis. These properties have made polyamines a potential target for therapeutic intervention in diseases of excessive cell proliferation such as cancer. However, attempts to limit tumor growth by inhibition of polyamine synthesis have not been very successful since cells have the capacity to take up polyamines from the bloodstream. We report here studies utilizing polyamine depletion by means of a combination of blockade of polyamine synthesis with DFMO (alpha-difluoromethylornithine), an inhibitor of ornithine decarboxylase, the rate limiting enzyme in the polyamine synthetic pathway, and ORI 1202, a novel inhibitor of polyamine transport into the cell. This cytostatic combination, even in the presence of excess extracellular polyamines, significantly slowed the growth of the human tumor cell line PC-3 grown in tissue culture with an EC(50) in the &mgr;M range. Other prostate cell lines were similarly growth inhibited including LNCaP.FGC and DU145. Growth of the PC-3 tumor cell line as a xenograft in nude mice was also slowed significantly by this combination of compounds. Polyamine levels in the tumor were lowered from control tumor levels. This combination therapy could provide an effective and potentially non-toxic therapy for prostate tumors.Prostate Cancer and Prostatic Diseases (2000) 3, 275-279 More... »

PAGES

4500420

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.pcan.4500420

DOI

http://dx.doi.org/10.1038/sj.pcan.4500420

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1011980478

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12497077


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