Structural and functional relationship among diamines in terms of inhibition of cell growth.
Following the report that agmatine has an anti-proliferative effect on cell growth through induction of antizyme [Satriano et al. (1998) J. Biol. Chem. 273, 15313-15316], we examined the effects of 16 different diamines on cell growth. Many diamines had little or no effect on cell growth, but agmatine and 1,6-hexanediamine had anti-proliferative effects, with agmatine having the strongest effect. Inhibition of cell growth occurred after 2 days, and inhibitory effects paralleled the degree of antizyme induction. Decreased spermine levels indicated that induction of spermidine/spermine N(1)-acetyltransferase was also involved in the inhibition of cell growth by agmatine and 1,6-hexanediamine. The frameshift efficiency (ratio of antizyme synthesis with or without frameshift) measured in a rabbit reticulocyte cell-free system was also increased by 1,3-propanediamine and cis-1,4-cyclohexanediamine in addition to agmatine and 1,6-hexanediamine. However, the intracellular levels of 1,3-propanediamine and cis-1,4-cyclohexanediamine were low when these compounds were added to the cell-culture medium. Other diamines had no effect on cell growth or frameshift efficiency. The results suggest that the presence of two amino-groups separated by an appropriate distance is important for the enhancement of frameshifting by diamines.
Higashi
Kyohei
K
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. iga16077@p.chiba-u.ac.jp
Yoshida
Kaori
K
Nishimura
Kazuhiro
K
Momiyama
Emi
E
Kashiwagi
Keiko
K
Matsufuji
Senya
S
Shirahata
Akira
A
Igarashi
Kazuei
K
D000081:Acetamides / Q000494:pharmacology; D000123:Acetyltransferases / Q000737:chemistry; D000376:Agmatine / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002474:Cell-Free System; D002478:Cells, Cultured; D003514:Cyclohexylamines / Q000494:pharmacology; D003959:Diamines / Q000494:pharmacology; D016368:Frameshift Mutation; D008956:Models, Chemical; D008958:Models, Molecular; D011073:Polyamines / Q000737:chemistry; D011700:Putrescine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors; D000099228:Diamine N-Acetyltransferase
D000081:Acetamides; D000123:Acetyltransferases; D000376:Agmatine; D003514:Cyclohexylamines; D003959:Diamines; D011073:Polyamines; D011700:Putrescine; D000099228:Diamine N-Acetyltransferase; C050895:N-acetyl-1,6-diaminohexane; C009475:trimethylenediamine