Angiotensin II and its fragments (angiotensins III and IV) decrease the growth of DU-145 prostate cancer in vitro.

BACKGROUND: There is growing evidence that angiotensin II (AngII) and its smaller fragments 2-8 (AngIII) and 3-8 (AngIV) are involved in cell-growth control in the vascular smooth muscle and in some other tissues, including prostate. The aim of this paper was to investigate the effects of AngII and its fragments AngIII and AngIV on the growth of an androgen-independent human prostate cancer cell line in vitro. To see whether the conversion of Ang II into its shorter fragments plays a role in the action of the former, we used specific inhibitors of aminopeptidases: compound EC33 (inhibitor of aminopeptidase A), which blocks the conversion of AngII into AngIII, and compound PC 18 (inhibitor of aminopeptidase N), which blocks the conversion of AngIII into AngIV. MATERIAL/METHODS: Human prostate cancer DU-145 cells were exposed in culture to different concentrations of AngII, AngIII, and AngIV separately or jointly with the aminopeptidase inhibitors EC33 or PC18. To measure cell growth, the colorimetric method, based on the reduction of tetrazolium salt by viable cells, was applied. RESULTS: It was found that exposure of DU-145 cells in vitro to all the investigated angiotensins resulted in a moderate, concentration-dependent inhibition of cell growth. The joint exposure of DU-145 cells to AngII plus EC33, but not to AngII plus PC 18, abolished the effect of AngII. CONCLUSIONS: These findings suggest that angiotensin peptides (AngII as well as its smaller fragments) are involved in the negative control of prostate cancer cell growth.

Keywords: Angiotensin II - analogs & derivatives, Angiotensin II - therapeutic use, Angiotensin III - therapeutic use, Glutamyl Aminopeptidase - antagonists & inhibitors, Sulfonic Acids - pharmacology, Angiotensin II - therapeutic use, Angiotensin III - therapeutic use, Cell Line, Tumor, Glutamyl Aminopeptidase - antagonists & inhibitors, Prostatic Neoplasms - drug therapy, Sulfonic Acids - pharmacology