Differential sensitivity of various human tumors to inhibition of polyamine biosynthesis in vivo

R. Saydjari, R. W. Alexander, J. R. Upp, S. C. Barranco, Courtney Townsend, J. C. Thompson

Research output: Contribution to journalArticle

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Abstract

Polyamines are essential for normal and neoplastic growth. Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme in the polyamine biosynthetic pathway. α-Difluoromethylornithine (DFMO) is an enzyme-activated irreversible inhibitor of ODC, and a known anti-neoplastic agent. The purpose of this study was to examine the susceptibility of various human cancers to inhibition by DFMO in vivo. We have studied three human pancreatic adenocarcinomas, designated CAV, SKI, and PGER, two human colon adenocarcinomas (LS-180 and WIDR), and three metastatic cell lines of a human gastric adenocarcinoma (BHM, BMM, BLM) that were growing in congenitally athymic (nude) Balb/c mice. Mice bearing each tumor were divided into two groups; one group served as controls and the other group received DFMO 3% in drinking water. Tumor growth and weight, and content of DNA, RNA, protein and polyamines were determined and correlated. DFMO significantly inhibited the growth of three of the three gastric tumors, two of the three pancreatic tumors and neither of the two colon tumors. The tumor content of DNA, RNA and protein exhibited a pattern that was parallel to tumor growth. The tumor polyamine concentration did not correlate with sensitivity to DFMO. These findings provide clear evidence for important differences in the sensitivity of various human cancers to growth inhibition by DFMO and indicate that endogenous polyamine levels alone do not predict the sensitivity of the tumors to DFMO.

Original languageEnglish (US)
Pages (from-to)44-48
Number of pages5
JournalInternational Journal of Cancer
Volume47
Issue number1
DOIs
StatePublished - 1991

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Polyamines
Eflornithine
Neoplasms
Growth
Adenocarcinoma
Stomach
Colon
RNA
Ornithine Decarboxylase
DNA
Biosynthetic Pathways
Enzymes
Tumor Burden
Drinking Water
Proteins
Cell Line
Control Groups

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Differential sensitivity of various human tumors to inhibition of polyamine biosynthesis in vivo. / Saydjari, R.; Alexander, R. W.; Upp, J. R.; Barranco, S. C.; Townsend, Courtney; Thompson, J. C.

In: International Journal of Cancer, Vol. 47, No. 1, 1991, p. 44-48.

Research output: Contribution to journalArticle

Saydjari, R. ; Alexander, R. W. ; Upp, J. R. ; Barranco, S. C. ; Townsend, Courtney ; Thompson, J. C. / Differential sensitivity of various human tumors to inhibition of polyamine biosynthesis in vivo. In: International Journal of Cancer. 1991 ; Vol. 47, No. 1. pp. 44-48.
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