Direct inhibitory effect of somatostatin on the growth of the human prostatic cancer cell line LNCaP: possible mechanism of action.
The effects of somatostatin-14 (S) on the proliferation of the human prostatic cancer cell line (LNCaP, lymph node carcinoma of the prostate) and on the amount of proteins secreted by these cells have been studied. LNCaP cells were treated for 3 days with different doses of S. The hormone significantly inhibits cell proliferation at doses comprised between 0.4 and 2 nmol, as indicated by a significant decrease in the incorporation of 3H-thymidine as well as in the uptake of [alpha-32P]dATP. The direct antiproliferative effect of S is reversible, since cell proliferation returns to normal 4 days after withdrawal of the hormone from the medium. This action of S is not due to cytotoxic side-effects, since no changes in the incorporation of 35S-methionine are observed. Total RNA and protein synthesis do not appear to be modified by the hormone in vitro. The hormone probably exerts its antiproliferative effect on LNCaP cells by stimulating phosphotyrosyl protein phosphatases, since the inhibition of growth induced by S (1 nmol) is reversed by sodium vanadate (2 and 4 mumol), a potent inhibitor of the process of tyrosine dephosphorilation. In addition, S (1 nmol/L) induces a significant decrease in the amounts of proteins secreted by LNCaP cells. Also the antisecretory action of S seems to be mediated by the activation of phosphotyrosyl protein phosphatases, since sodium vanadate is able to reverse the action of S on this parameter. In conclusion, the present data suggest for the first time that S exerts a direct inhibitory effect on LNCaP cell proliferation and protein secretion, two effects probably mediated by the activation of phosphotyrosyl protein phosphatases.
Brevini
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TA
Department of Endocrinology, University of Milano, Italy.
Bianchi
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Motta
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D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008297:Male; D008715:Methionine / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D013004:Somatostatin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
D003838:Deoxyadenine Nucleotides; D011506:Proteins; D014638:Vanadates; D013004:Somatostatin; D012313:RNA; D004247:DNA; D008715:Methionine; C026600:2'-deoxyadenosine triphosphate; D014529:Uridine