Correlation between the effects of bombesin antagonists on cell proliferation and intracellular calcium concentration in Swiss 3T3 and HT-29 cell lines

Felipe F. Casanueva, Francisco R. Perez, Xesus Casabiell, Jesus P. Camiña, Ren Zhi Cai, Andrew V. Schally

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Bombesin (BN) acts as an autocrine mitogen in various human cancers. Several pseudononapeptide BN-(6-14) analogs with a reduced peptide bond between positions 13 and 14 have been shown to suppress the mitogenic activity of BN or gastrin-releasing peptide (GRP) when assessed by radioreceptor or proliferation assays and may have significant clinical applications. The search for potent and safe BN antagonists requires the evaluation of a large series of analogs in radioreceptor and proliferation assays. In this paper, we report that the ability of BN analogs to inhibit BN-induced calcium transients in Swiss 3T3 cells shows a high correlation with their inhibitory potency as evaluated by classical proliferation tests. The assay of calcium transients allows a rapid characterization of new BN analogs (in terms of minutes rather than days) and can be adapted as a labor and cost-effective screening step in the selection of potentially relevant BN antagonists for further characterization in cell proliferation systems. We also observed that results from the assay of calcium transients in Swiss 3T3 cells can be correlated with the results of the proliferative response in HT- 29 cells, a cell line that does not seem to use the same early transmembrane ionic signal system. This result suggests that the calcium pathway is not mandatory for triggering cell division by the BN receptor.

Original languageEnglish (US)
Pages (from-to)1406-1411
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number4
DOIs
StatePublished - Feb 20 1996

Keywords

  • bombesin analog evaluation
  • calcium pathway
  • mitogenic activity
  • transmembrane signaling

ASJC Scopus subject areas

  • Genetics
  • General

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