Isolation and characterization of human breast adenocarcinoma cells made resistant to alpha-difluoromethylornithine.

Abstract

Human breast adenocarcinoma cells MCF-7 were selected for resistance to ornithine decarboxylase (ODC) inhibitor, alpha-difluoromethylornithine (DFMO). Stepwise increments of the concentration of DFMO resulted in selection of MCF-7 cells that were capable of growing in the presence of 1.0 mM DFMO. This capacity was associated with a 10-fold increase in ODC activity and marked enhancement in the synthesis rate of ODC protein as verified by a 2-hr [35S]methionine labeling of cellular proteins followed by immunoprecipitation and SDS-PAGE. The resistant cells had much higher concentration of putrescine, spermidine, and spermine than the control cells. A 25-fold increase in ED50 (effective dose causing 50% inhibition) for the antiproliferative action of DFMO in these resistant cells was observed. The susceptibility of wild-type and resistant cell lines to other inhibitors of the polyamine biosynthetic pathway and adriamycin is also reported.

• Authors: B Das, M Vig, K K Khurana, R Madhubala
• Journal: Cancer investigation (Cancer Invest) Vol. 18 Issue 2 Pg. 115-22 ( 2000) ISSN: 0735-7907 [Print] England
• PMID: 10705873 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• Ornithine Decarboxylase Inhibitors
• Polyamines
• Ornithine Decarboxylase
• Eflornithine

Topics

• Adenocarcinoma (drug therapy, metabolism, pathology)
• Antineoplastic Agents (pharmacology)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm
• Drug Screening Assays, Antitumor
• Eflornithine (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Humans
• Ornithine Decarboxylase (metabolism)
• Ornithine Decarboxylase Inhibitors
• Polyamines (metabolism)
• Tumor Cells, Cultured