Polyamines and prostatic cancer.
The importance of polyamines in prostatic growth and differentiation has prompted studies to evaluate the clinical relevance of the ornithine decarboxylase/polyamine system in prostatic cancer. These studies show that differences in biological behaviour of prostatic (cancer) cells are associated with changes in polyamine levels and/or the activity of their metabolic enzymes. Faulty antizyme regulation of polyamine homoeostasis may play an important role in the growth and progression of prostatic carcinoma. Treatment of human prostate carcinoma cells with inhibitors of polyamine metabolic enzymes or polyamine analogues induces cell growth arrest or (apoptotic) cell death. Our recent in vitro studies using conformationally restricted polyamine analogues show that these compounds inhibit cell growth, probably by inducing antizyme-mediated degradation of ornithine decarboxylase. Sensitivity of human prostate cancer cells for these compounds was increased in the absence of androgens. These results suggest that these analogues might have chemotherapeutic potential in case prostatic cancer has become androgen-independent. Pilot data in an in vivo model show that these analogues have effects on tumour cell proliferation, vascularity, blood perfusion and tissue hypoxia. Overall, these studies show that polyamines may serve as important biomarkers of prostatic malignancy and provide a promising target for chemotherapy of prostatic cancer.
Schipper
R G
RG
Department of Pathology, University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. r.schipper@pathol.umcn.nl
Romijn
J C
JC
Cuijpers
V M J I
VM
Verhofstad
A A J
AA
D000970:Antineoplastic Agents / Q000494:pharmacology; D015317:Biogenic Polyamines / Q000037:antagonists & inhibitors / Q000502:physiology*; D014408:Biomarkers, Tumor; D002455:Cell Division / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*
D000970:Antineoplastic Agents; D015317:Biogenic Polyamines; D014408:Biomarkers, Tumor