Abstract
5'-Methylthioadenosine is a sulfur-containing nucleoside derived from the metabolism of polyamines which is known to exert an antiproliferative effect on several cell systems in vitro, including the Friend leukemia cell system. We have investigated the role of 5'-methylthioadenosine on the dimethyl sulfoxide-induced differentiation of this system. At a concentration of 400 μM, the drug strongly inhibited (80%) the induced differentiation of Friend cells, and this effect was already observable at a concentration as low as 10 μM (36% inhibition), as evidenced by the benzidine staining procedure and by the dot-blot hybridization of globin mRNA with a human β-globin probe. Similar results have been obtained by using 5'-S-isobutylthioadenosine, which is a synthetic structural analogue of 5'-methylthioadenosine. The block of differentiation produced by these nucleosides was not mediated by adenine (a catabolite of both molecules) and was not reverted by spermine or spermidine, the two polyamines whose synthesis is inhibited by 5'-methylthioadenosine. We report a decrease of the aminopropyltransferases activities (the enzymes responsible for 5'-methylthioadenosine biosynthesis) in dimethyl sulfoxide-treated Friend cells, which could lead to a decrease of the intracellular content of 5'-methylthioadenosine during the erythroid maturation of Friend cells. The results obtained are consistent with the hypothesis that 5'-methylthioadenosine may act as an endogenous regulator of Friend cell differentiation.
| Original language | English |
|---|---|
| Pages (from-to) | 4096-4103 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 44 |
| Issue number | 9 |
| Publication status | Published - 1984 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Inhibition of dimethyl sulfoxide-induced differentiation of Friend erythroleukemic cells by 5'-methylthioadenosine. / Di Fiore, P. P.; Grieco, M.; Pinto, A.; Attadia, V.; Porcelli, M.; Cacciapuoti, G.; Cartenì-Farina, M.
In: Cancer Research, Vol. 44, No. 9, 1984, p. 4096-4103.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of dimethyl sulfoxide-induced differentiation of Friend erythroleukemic cells by 5'-methylthioadenosine
AU - Di Fiore, P. P.
AU - Grieco, M.
AU - Pinto, A.
AU - Attadia, V.
AU - Porcelli, M.
AU - Cacciapuoti, G.
AU - Cartenì-Farina, M.
PY - 1984
Y1 - 1984
N2 - 5'-Methylthioadenosine is a sulfur-containing nucleoside derived from the metabolism of polyamines which is known to exert an antiproliferative effect on several cell systems in vitro, including the Friend leukemia cell system. We have investigated the role of 5'-methylthioadenosine on the dimethyl sulfoxide-induced differentiation of this system. At a concentration of 400 μM, the drug strongly inhibited (80%) the induced differentiation of Friend cells, and this effect was already observable at a concentration as low as 10 μM (36% inhibition), as evidenced by the benzidine staining procedure and by the dot-blot hybridization of globin mRNA with a human β-globin probe. Similar results have been obtained by using 5'-S-isobutylthioadenosine, which is a synthetic structural analogue of 5'-methylthioadenosine. The block of differentiation produced by these nucleosides was not mediated by adenine (a catabolite of both molecules) and was not reverted by spermine or spermidine, the two polyamines whose synthesis is inhibited by 5'-methylthioadenosine. We report a decrease of the aminopropyltransferases activities (the enzymes responsible for 5'-methylthioadenosine biosynthesis) in dimethyl sulfoxide-treated Friend cells, which could lead to a decrease of the intracellular content of 5'-methylthioadenosine during the erythroid maturation of Friend cells. The results obtained are consistent with the hypothesis that 5'-methylthioadenosine may act as an endogenous regulator of Friend cell differentiation.
AB - 5'-Methylthioadenosine is a sulfur-containing nucleoside derived from the metabolism of polyamines which is known to exert an antiproliferative effect on several cell systems in vitro, including the Friend leukemia cell system. We have investigated the role of 5'-methylthioadenosine on the dimethyl sulfoxide-induced differentiation of this system. At a concentration of 400 μM, the drug strongly inhibited (80%) the induced differentiation of Friend cells, and this effect was already observable at a concentration as low as 10 μM (36% inhibition), as evidenced by the benzidine staining procedure and by the dot-blot hybridization of globin mRNA with a human β-globin probe. Similar results have been obtained by using 5'-S-isobutylthioadenosine, which is a synthetic structural analogue of 5'-methylthioadenosine. The block of differentiation produced by these nucleosides was not mediated by adenine (a catabolite of both molecules) and was not reverted by spermine or spermidine, the two polyamines whose synthesis is inhibited by 5'-methylthioadenosine. We report a decrease of the aminopropyltransferases activities (the enzymes responsible for 5'-methylthioadenosine biosynthesis) in dimethyl sulfoxide-treated Friend cells, which could lead to a decrease of the intracellular content of 5'-methylthioadenosine during the erythroid maturation of Friend cells. The results obtained are consistent with the hypothesis that 5'-methylthioadenosine may act as an endogenous regulator of Friend cell differentiation.
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UR - http://www.scopus.com/inward/citedby.url?scp=0021162156&partnerID=8YFLogxK
M3 - Article
C2 - 6611203
AN - SCOPUS:0021162156
VL - 44
SP - 4096
EP - 4103
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 9
ER -