TY - JOUR
T1 - The comparative effects of 5′-methylthioadenosine and some of its analogs on cells containing, and deficient in, 5′-methylthioadenosine phosphorylase
AU - White, Michael W.
AU - Riscoe, Michael K.
AU - Ferro, Adolph J.
N1 - Funding Information:
This investigationw as supported by grant CA25756 from the National Cancer Institute. A.J,F. is a recipiento f a Public Health Service CareerD evelopmenAtw ard (CA 00617)f rom the National Instituteso f Health. Partial supportf or M.W.W. and M.K.R. was from the N.L. Tarter ResearchF ellowshipF und.
PY - 1983/6/2
Y1 - 1983/6/2
N2 - The antiproliferative effects of 5′-methylthioadenosine and the 5′-methylthioadenosine analogs, 5′-isobutylthioadenosine, 5′-deoxyadenosine and 5′-methylthiotubercidin were examined using two mouse cell lines, one 5′-methylthioadenosine phosphorylase-deficient the other containing 5′-methylthioadenosine phosphorylase. All of the compounds were found to be growth inhibitory to both cell lines, demonstrating that these compounds need not be degraded to exert their inhibitory effects. A correlation was observed between the potency of the growth inhibitory effect and the ability of the cells to degrade these compounds. 5′-Methylthioadenosine, 5′-deoxyadenosine and 5′-isobutylthioadenosine, all of which are substrates for the 5′-methylthioadenosine phosphorylase in vitro, were more growth inhibitory to the 5′-methylthioadenosine phosphorylase-deficient cells than to the 5′-methylthioadenosine phosphorylase-containing cells, whereas, the 7-deaza analog, 5′-methylthiotubercidin, a nondegradable inhibitor of the 5′-methylthioadenosine phosphorylase, was a more potent inhibitor of the 5′-methylthioadenosine phosphorylase-containing cell line. Due to the inhibition by 5′-methylthiotubercidin on 5′-methylthioadenosine phosphorylase in vitro the disposition of cellularly-synthesized 5′-methylthioadenosine was explored using both cell types. 5′-Methylthiotubercidin inhibited the accumulation of exogenous 5′-methylthioadenosine from 5′-methylthioadenosine phosphorylase-deficient cells with no effect on intracellular 5′-methylthioadenosine. In contrast, 5′-methylthiotubercidin caused a large accumulation of extracellular 5′-methylthioadenosine with a concomitant smaller increase intracellularly in 5′-methylthioadenosine phosphorylase-containing cells. That cellularly-synthesized 5′-methylthioadenosine as well as the cellular excretion of this nucleoside are altered in response to treatment with 5′-methylthiotubercidin suggests two possible sites at which 5′-methylthiotubercidin may exert its effect.
AB - The antiproliferative effects of 5′-methylthioadenosine and the 5′-methylthioadenosine analogs, 5′-isobutylthioadenosine, 5′-deoxyadenosine and 5′-methylthiotubercidin were examined using two mouse cell lines, one 5′-methylthioadenosine phosphorylase-deficient the other containing 5′-methylthioadenosine phosphorylase. All of the compounds were found to be growth inhibitory to both cell lines, demonstrating that these compounds need not be degraded to exert their inhibitory effects. A correlation was observed between the potency of the growth inhibitory effect and the ability of the cells to degrade these compounds. 5′-Methylthioadenosine, 5′-deoxyadenosine and 5′-isobutylthioadenosine, all of which are substrates for the 5′-methylthioadenosine phosphorylase in vitro, were more growth inhibitory to the 5′-methylthioadenosine phosphorylase-deficient cells than to the 5′-methylthioadenosine phosphorylase-containing cells, whereas, the 7-deaza analog, 5′-methylthiotubercidin, a nondegradable inhibitor of the 5′-methylthioadenosine phosphorylase, was a more potent inhibitor of the 5′-methylthioadenosine phosphorylase-containing cell line. Due to the inhibition by 5′-methylthiotubercidin on 5′-methylthioadenosine phosphorylase in vitro the disposition of cellularly-synthesized 5′-methylthioadenosine was explored using both cell types. 5′-Methylthiotubercidin inhibited the accumulation of exogenous 5′-methylthioadenosine from 5′-methylthioadenosine phosphorylase-deficient cells with no effect on intracellular 5′-methylthioadenosine. In contrast, 5′-methylthiotubercidin caused a large accumulation of extracellular 5′-methylthioadenosine with a concomitant smaller increase intracellularly in 5′-methylthioadenosine phosphorylase-containing cells. That cellularly-synthesized 5′-methylthioadenosine as well as the cellular excretion of this nucleoside are altered in response to treatment with 5′-methylthiotubercidin suggests two possible sites at which 5′-methylthiotubercidin may exert its effect.
KW - (Mouse cell)
KW - Methylthioadenosine
KW - Methylthioadenosine phosphorylase
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U2 - 10.1016/0167-4889(83)90005-8
DO - 10.1016/0167-4889(83)90005-8
M3 - Article
C2 - 6405800
AN - SCOPUS:0021093357
SN - 0167-4889
VL - 762
SP - 405
EP - 413
JO - BBA - Molecular Cell Research
JF - BBA - Molecular Cell Research
IS - 3
ER -