Biochemical effects and growth inhibition in MCF-7 cells caused by novel sulphonamido oxa-polyamine derivatives.

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.

• 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)

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

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