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 pM, 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 microM 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.
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Authors | V Pavlov, P Kong Thoo Lin, V Rodilla |
Journal | Cellular and molecular life sciences : CMLS
(Cell Mol Life Sci)
Vol. 59
Issue 4
Pg. 715-23
(Apr 2002)
ISSN: 1420-682X [Print] Switzerland |
PMID | 12022477
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Polyamines
- Sulfonamides
- sulfonamido oxa-spermidine
- sulfonamido oxa-spermine
- Spermine
- Amine Oxidase (Copper-Containing)
- Oxidoreductases Acting on CH-NH Group Donors
- polyamine oxidase
- Spermidine
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Topics |
- Amine Oxidase (Copper-Containing)
(metabolism)
- Antineoplastic Agents
(pharmacology, toxicity)
- Apoptosis
- Breast Neoplasms
(drug therapy, metabolism, pathology)
- Cell Division
- Cell Nucleus
(drug effects, ultrastructure)
- DNA Fragmentation
- Dose-Response Relationship, Drug
- Drug Screening Assays, Antitumor
- Female
- Humans
- Microscopy, Phase-Contrast
- Oxidoreductases Acting on CH-NH Group Donors
(metabolism)
- Polyamines
(metabolism)
- Spermidine
(analogs & derivatives, chemistry, pharmacology, toxicity)
- Spermine
(analogs & derivatives, chemistry, pharmacology, toxicity)
- Sulfonamides
(chemistry, pharmacology, toxicity)
- Tumor Cells, Cultured
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