title: The DDAH/NOS pathway in human prostatic cancer cell lines: antiangiogenic effect of L-NAME.
abstract: Benign prostate hypertrophy (BPH) and prostate cancer (PC) are prostate chronic diseases that require a long period for development from a small lesion to clinical manifestation. PC is the most common cancer in men in Europe and the Americas. Tumor growth and metastasis depend upon the development of neovasculature around the tumor. This process, called angiogenesis, may be regulated by NO, and thus modulation of NO production could play an important role in tumor progression. Recent studies report the involvement of DDAH, an enzyme which metabolizes the endogenous NOS inhibitor ADMA, in the development of tumor vasculature. The aim of the present study was to verify the involvement of the DDAH/NOS pathway in the progression of prostate cancer. The effect of the NOS inhibitor L-NAME was evaluated in the human prostate cancer cell line LnCap and in BPH-1 cells which represent benign prostatic hypertrophy. Higher DDAH-2, eNOS, iNOS and VEGF expression was found in LnCap cells compared to BPH-1 cells. L-NAME treatment of LnCap cells resulted in a reduction in VEGF, iNOS and eNOS expression. VEGF, iNOS and eNOS inhibition is a promising approach for targeting tumor vasculature and certain NOS inhibitors could potentially serve as experimental agents for treatment of certain chemoresistant tumors, including prostate tumors. Moreover, since in our experimental conditions L-NAME was unable to reduce DDAH activity and expression, it is plausible to hypothesize the development of a targeted polypharmacological approach by developing dual and specific inhibitors of DDAH and NOS to better control NO biosynthesis.
authors: Dipartimento di Scienze del Farmaco, Sezione di Biochimica, Università di Catania, I-95125 Catania, Italy.
authors: Luca
authors: L
authors: Vanella
authors: Claudia
authors: C
authors: Di Giacomo
authors: Rosaria
authors: R
authors: Acquaviva
authors: Rosa
authors: R
authors: Santangelo
authors: Venera
authors: V
authors: Cardile
authors: Ignazio
authors: I
authors: Barbagallo
authors: Nader G
authors: NG
authors: Abraham
authors: Valeria
authors: V
authors: Sorrenti
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D042461:Vascular Endothelial Growth Factor A; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; C059999:dimethylargininase; D019331:NG-Nitroarginine Methyl Ester