Decrease of polyamine levels and enhancement of transglutaminase activity in selective reduction of B16-F10 melanoma cell proliferation induced by atrial natriuretic peptide.
The atrial natriuretic peptide (ANP) at physiological levels reduced the proliferation of highly metastatic murine (B16-F10) and human (SK-MEL 110) melanoma cell lines whereas rat aortic smooth muscle (RASM) cells were unaffected. In RASM cells, the levels of proliferation markers (putrescine, spermidine and spermine) increase after 24 h of epidermal growth factor (EGF) stimulation (RASM-EGF), but strongly decrease after 24 h of exposition to ANP. The B16-F10 cell line, which received no EGF stimulation, showed a similar decrease in polyamine content after ANP treatment. Furthermore, the enzymatic activity of a differentiation marker (transglutaminase) was increased for both RASM-EGF and B16-F10 cells after 24 h of treatment with 10(-10) mol/l ANP, concomitantly with the observed inhibition of polyamine biosynthesis and cell growth. Data obtained on B16-F10 cells treated with 8Br-GMPc or with an ANP analogue (cANF) support the involvement of the type C ANP receptor (NRP-C) in hormone effects. From the overall results, it appears that ANP may play a role in the inhibition of cellular growth under hyperproliferative conditions, as shown for RASM-EGF cells. The B16-F10 melanoma cell line showed similar results, but in the absence of mitogen stimulation. This observation suggests that the constitutive hyperproliferative state of tumor cells may be a sufficient condition to favor the ANP inhibitory effects on cell growth. This finding is particularly interesting in the light of a possible use of ANP as a potential selective antineoplastic agent.
Baldini
Patrizia M
PM
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Lentini
Alessandro
A
Mattioli
Palma
P
Provenzano
Bruno
B
De Vito
Paolo
P
Vismara
Daniela
D
Beninati
Simone
S
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D008297:Male; D008543:Melanins / Q000378:metabolism; D008546:Melanoma, Experimental / Q000201:enzymology* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D045283:Natriuretic Agents / Q000494:pharmacology; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism*
D008543:Melanins; D045283:Natriuretic Agents; D011073:Polyamines; D020098:Natriuretic Peptide, C-Type; D013096:Spermine; D004815:Epidermal Growth Factor; D009320:Atrial Natriuretic Factor; D011503:Transglutaminases; D013095:Spermidine; D011700:Putrescine