Isolation of a polyamine transport deficient cell line from the human non-small cell lung carcinoma line NCI H157

Dan Shao, Lei Xiao, Hyo Chol Ha, Robert A. Casero

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

In an effort to study the mechanism underlying the observed phenotype-specific response of human lung cancer cell lines to a polyamine analogue, N1,N12-bis(ethyl)spermine(BESpm), we have isolated a BESpm resistant cell line from the BESpm-sensitive large cell lung carcinoma line NCI H157. The mutant line exhibits identical growth rates in the presence or absence of the analogue. However, the overall growth of mutant cells reaches stationary phase earlier than that of the parental cells. In contrast to the parental cells, where a superinduction of spermidine/spermine N1-acetyltransferase (SSAT) is associated with BESpm toxicity, treatment of this resistant line with BESpm did not induce SSAT mRNA or enzyme activity. BESpm treatment was not effective in depleting the intracellular polyamine pools and very low intracellular BESpm levels were detected. This BESpm resistance is not mediated by multidrug resistance (MDR) protein, since these cells maintain their sensitivity to the antineoplastic agent adriamycin. Treatment of these cells with methylglyoxal bis(guanylhydrazone) (MCBG), an AdoMetDC inhibitor which enters cell using polyamine transport system, shows no inhibition of cell growth. Our data suggest that these mutant cells are deficient in polyamine transport. Consistent with this hypothesis, exogenous polyamines did not prevent difluoromethylornithine (DFMO) induced growth inhibition in the mutant cells.

Original languageEnglish (US)
Pages (from-to)43-48
Number of pages6
JournalJournal of Cellular Physiology
Volume166
Issue number1
DOIs
StatePublished - Jan 1996

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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