Effect of herbimycin A on growth and pp60(c-src) activity in human colon tumor cell lines

R. Garcia, N. U. Parikh, H. Saya, G. E. Gallick

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Abstract

The effect of herbimycin A, an ansamycin antibiotic which inhibits cellular transformation by retroviral tyrosine kinases, on the monolayer growth of seven colon tumor cell lines and one cell line established from normal colonic mucosa, CCL239, was examined. Each colon tumor cell line tested showed dose-dependent growth inhibition in response to herbimycin A. A 125 ngml-1 dose of the antibiotic caused > 40% growth inhibition in all colon tumor cell lines after two cell doublings. In contrast, at similar herbimycin A concentrations only 12% inhibition was observed in 'normal' CCL239 cells. No major morphologic changes were observed at the light microscopic level in any of the tumor cell lines or CCL239 cells in response to treatment with herbimycin A. Studies using the HT29 colon adenocarcinoma cell line showed dose-dependent inactivation of pp60(c-src) by herbimycin A, resulting in decreased autophosphorylation, enolase phosphorylation and steady-state levels, which correlated with cellular growth inhibition. Herbimycin A-induced reductions in pp60(c-src) kinase activity preceded changes in pp60(c-src) steady-state levels. Growth and pp60(c-src) inhibition were reversible following removal of herbimycin A from cell culture media. Our results suggest that regulation of pp60(c-src) tyrosine kinase activity may be important in growth control of colon tumor cells.

Original languageEnglish
Pages (from-to)1983-1989
Number of pages7
JournalOncogene
Volume6
Issue number11
Publication statusPublished - 29-11-1991
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Garcia, R., Parikh, N. U., Saya, H., & Gallick, G. E. (1991). Effect of herbimycin A on growth and pp60(c-src) activity in human colon tumor cell lines. Oncogene, 6(11), 1983-1989.