Potentiation of the growth inhibitory effects of adenosine 3',5'-monophosphate analogues by homocysteine.
The growth inhibitory effects of N6-monobutyryl adenosine 3',5'-monophosphate (mbcAMP) and N6,O2'-dibutyryl adenosine 3',5' monophosphate (dbcAMP) towards Walker carcinoma in vitro are significantly potentiated by the addition of L-homocysteine to the culture medium. This effect is not seen with L-cysteine or when exogenous cAMP or prostaglandin E2(PGE2) replace the butyrylated cyclic nucleotide. Combinations of mbcAMP or dbcAMP and L-homocysteine significantly inhibit nucleic acid methylations. Both the butyrylated cyclic nucleotides cause an elevation of the intracellular level of S-adenosyl-L-homocysteine (SAH), a potent inhibitor of S-adenosyl-L-methionine (SAM) dependent methyltransferases, and this is significantly enhanced in combination with L-homocysteine. The increase in SAH level produced by such combinations is proportional to the inhibition of methyl group incorporation into 5-methyl cytosine and 7-methyl guanine. These results suggest that L-homocysteine potentiates accumulation of SAH in the presence of mbcAMP and dbcAMP and that the resultant inhibition of methylation accounts for the enhanced growth inhibition.
D000818:Animals; D003994:Bucladesine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002279:Carcinoma 256, Walker / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004357:Drug Synergism; D006710:Homocysteine / Q000494:pharmacology*; D008745:Methylation; D012435:S-Adenosylhomocysteine / Q000032:analysis
D006710:Homocysteine; C002373:monobutyryl cyclic AMP; D003994:Bucladesine; D012435:S-Adenosylhomocysteine