Growth and biochemical effects of unsymmetrically substituted polyamine analogues in human lung tumor cells 1.

Abstract

Three unsymmetrically substituted polyamine analogues demonstrate significant and selective antitumor effects. Each of the analogues N1-ethyl-N11-propargyl-4,8-diazaundecane (PENSpm), N1-ethyl-N11-(cyclobutyl)methyl-4,8-diazaundecane (CBENSpm), and N1-ethyl-N11-(cyclopropyl)methyl-4,8-diazaundecane (CPENSpm) is cytotoxic to a representative non-small-cell lung carcinoma line, NCI H157, while being only growth-inhibitory to a representative small-cell-lung carcinoma line, NCI H82. Cytotoxicity is accompanied by a significant increase in expression of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT) at the levels of activity and steady-state mRNA. These new analogues are significant both for their cell-type-specific activity and as synthetic prototypes for the addition of SSAT-activated functional groups.

• Authors: R A Casero Jr, A R Mank, N H Saab, R Wu, W J Dyer, P M Woster
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 36 Issue 1 Pg. 69-74 ( 1995) ISSN: 0344-5704 [Print] Germany
• PMID: 7720179 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• N(1)-ethyl-N(11)-(cyclobutyl)methyl-4,8-diazaundecane-1,11-diamine
• Polyamines
• Acetyltransferases
• diamine N-acetyltransferase
• Ornithine Decarboxylase

Topics

• Acetyltransferases (metabolism)
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Dose-Response Relationship, Drug
• Humans
• Lung Neoplasms (drug therapy)
• Ornithine Decarboxylase (metabolism)
• Polyamines (therapeutic use)
• Structure-Activity Relationship
• Tumor Cells, Cultured (drug effects)