Effects of suramin on polyamine metabolism in B16 murine melanoma cells.
Polyamines and their biosynthetic enzymes, such as ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), are crucial for normal and neoplastic cell growth and differentiation. Suramin inhibits the growth of several tumor cells by affecting various intracellular targets, but its effects on polyamines are not known. In this study, the effects of suramin on some parameters of polyamine metabolism in B16 melanoma cells were investigated in vitro. Suramin increased cellular ODC activity and ODC mRNA levels, whereas the drug was directly inhibitory to the enzyme. AdoMetDC was not affected. Cellular putrescine levels were enhanced by suramin, whereas spermidine and spermine pools were unaltered. Cells cultured in the presence of suramin showed decreased cellular polyamine transport, but no direct inhibitory effect on the polyamine transporter could be found. Fluorescence spectroscopy demonstrated a direct interaction between suramin and spermine. It may be concluded that suramin affects polyamine metabolism, and that its effects in some respects are opposite to those of alpha-difluoromethylomithine (DFMO), a specific inhibitor of ODC.
Gritli-Linde
A
A
Department of Oral Biochemistry, Göteborg University, Sweden. linde@odontologi.gu.se
Björkman
U
U
Delle
U
U
Frostesjö
L
L
Hultborn
R
R
Hultén
K
K
Johansson
B R
BR
Nannmark
U
U
Linde
A
A
D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015317:Biogenic Polyamines / Q000378:metabolism*; D000518:Eflornithine / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D015317:Biogenic Polyamines; D013498:Suramin; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase; D000518:Eflornithine