Growth, morphological and biochemical changes in oxa-spermine derivative-treated MCF-7 human breast cancer cells.
The growth inhibitory properties of two oxa-spermine derivatives named compound 1 and compound 2, representatives of a novel type of polyamine derivatives, were studied. Dose-response growth inhibitory curves obtained after 48h drug exposure demonstrated the much higher cytotoxic activity of compound 1 towards MCF-7 human breast cancer cells. Further experiments with compound 1 showed that this oxa-spermine derivative exhibited considerable cytotoxicity with IC(50) values of 3.74 microM and 2.93 microM after 24h and 48h drug exposure respectively. In MCF-7 cells, after 8h drug (10 microM) exposure it caused shrinkage, chromatin condensation and nuclear fragmentation. However, no clear DNA laddering was detected in treated cells. Drug treatment provoked an increase in polyamine oxidase (PAO) activity. This enzyme is able to produce cytotoxic H(2)O(2) and 3-acetamidopropanal, catalyzing the oxidative deamination of N(1)-acetylated derivatives of spermine and spermidine to spermidine and putrescine respectively. Taken together these data demonstrate that the novel oxa-polyamine derivative compound 1 has considerable cytotoxic activity towards MCF-7 cells and indicate that an induction of PAO may be involved in its cytotoxic and apoptotic effects.
Pavlov
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Department of Human and Animal Physiology, Faculty of Biology, University of Sofia St. Kliment Ohridski, Dr. Tzankov Blvd. 8, 1164 Sofia, Bulgaria. vpavlov@biofac.uni-sofia.bg
Rodilla
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Kong Thoo Lin
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015317:Biogenic Polyamines / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000032:analysis / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000096:biosynthesis / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000097667:Polyamine Oxidase
D000970:Antineoplastic Agents; D015317:Biogenic Polyamines; D004273:DNA, Neoplasm; D000587:Oxidoreductases Acting on CH-NH Group Donors; D013096:Spermine; D000097667:Polyamine Oxidase