Biochemical effects and growth inhibition in MCF-7 cells caused by novel sulphonamido oxa-polyamine derivatives |
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Authors: | V Pavlov P Kong Thoo Lin V Rodilla |
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Affiliation: | (1) Department of Human and Animal Physiology, Faculty of Biology, University of Sofia 'St. Kliment Ohridski', Dr. Tzankov Blvd. 8, Sofia, 1164 (Bulgaria), BG;(2) The Robert Gordon University, School of Life Sciences, St. Andrew Street, Aberdeen, AB25 1HG (United Kingdom), GB;(3) Facultad de Ciencias Experimentales y de la Salud, Universidad Cardenal Herrera-CEU, Avda. Seminario, s/n, 46113 Moncada, Valencia (Spain), Fax + 44 96 139 52 72, e-mail: vrodilla@uch.ceu.es , ES |
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Abstract: | The novel polyamine derivatives sulphonamido oxa-spermine (oxa-Spm) and sulphonamido oxa-spermidine (oxa-Spd) exhibited rapid
cytotoxic action towards MCF-7 human breast cancer cells with IC50 values of 4.35 and 6.47 μM, respectively, after 24-h drug exposure. Neither compound is a substrate of serum amine oxidase.
Both oxa-Spm and oxa-Spd caused cell shrinkage, as determined by phase-contrast microscopy. After incubation with 10 μM of
either compound for 8 h, the cells underwent chromatin condensation and nuclear fragmentation. However, no clear DNA ladder
was obtained by electrophoresis. The sulphonamido oxa-polyamine derivatives and especially oxa-Spd enhanced the activity of
polyamine oxidase (PAO), an enzyme capable of oxidising N1-acetylated spermine and spermidine to spermidine and putrescine, respectively, generating cytotoxic H2O2 and 3-acetamidopropanal as by-products. The intracellular polyamine content was only marginally reduced in response to drug
treatment. In conclusion, our data show that these novel sulphonamido oxa-polyamine derivatives possess high cytotoxic activity
against MCF-7 cells and indicate that induction of PAO may mediate their cytotoxicity via apoptosis.
Received 17 January 2002; received after revision 22 February 2002; accepted 22 February 2002 |
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Keywords: | , Polyamine derivative, cytotoxicity, MCF-7 cell, apoptosis, polyamine oxidase, polyamine, |
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