Effects of polyamine synthesis inhibitors on primary tumor features and metastatic capacity of human breast cancer cells

Andrea Manni, Sharlene Washington, Xin Hu, James W. Griffith, Richard Bruggeman, Laurence M. Demers, David Mauger, Michael F. Verderame

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


We have previously reported that inhibition of polyamine biosynthesis with α-difluoromethylornithine (DFMO) reduces pulmonary metastasis from MDA-MB-435 human breast cancer xenografts without affecting the volume of the primary tumors (Manni et al. Clin Exp Mets 20:321, 2003). In these experiments, we show that DFMO treatment (2% in drinking H2O) reduced the growth fraction of the primary tumors by 60%. However, this effect was counter-balanced by a similar reduction in non-apoptotic necrosis, thus accounting for the preservation of tumor volume in DFMO-treated mice. DFMO treatment caused a 4-fold increase in cytoplasmic staining for cleaved caspase-3 (as opposed to the nuclear staining observed in control tonsil tissue) in the absence of histologic evidence of apoptosis. DFMO treatment reduced the number of mice with pulmonary metastasis by 80% and the number of metastasis per mouse by 90% in association with a reduction in invasiveness of the primary tumor in the surrounding dermis and muscle by 30%. DFMO treatment increased ERK phosphorylation in the tumors, an effect that has been found by us in vitro to be causally linked to the anti-invasive effect of the drug (Manni et al. Clin Exp Metast 2004; 21: 461]. DFMO also increased tyrosine phosphorylation of STAT-3 and expression of STAT-1 and JNK proteins. Administration of SAM486A (1 mg/kg/ip daily), an inhibitor of S-adenosylmethionine decarboxylase, either individually or in combination with DFMO, was not found to exert any biological or biochemical effects, most likely as a result of its failure to suppress tissue polyamine levels under these experimental conditions.

Original languageEnglish (US)
Pages (from-to)255-263
Number of pages9
JournalClinical and Experimental Metastasis
Issue number3
StatePublished - Jan 2005

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


Dive into the research topics of 'Effects of polyamine synthesis inhibitors on primary tumor features and metastatic capacity of human breast cancer cells'. Together they form a unique fingerprint.

Cite this