Effect of the cytostatic butyric acid pro-drug, pivaloyloxymethyl butyrate, on the tumorigenicity of cancer cells

Adina Aviram*, Ada Rephaeli, Mati Shaklai, Abraham Nudelman, Irit Ben-Dror, Lea Maron, Esther Rabizadeh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Previously we have shown that pivaloyloxymethyl butyrate (AN-9), a pro-drug of butyric acid (BA), is a differentiation-inducing agent in a variety of cells. In this report, we demonstrate that AN-9 is a cytostatic but not cytotoxic agent in a myelomonocytic cell line (WEHI); thus, the cells were growth-arrested and differentiated. These late changes in the cells were preceded by changes in the expression of the early regulatory genes, c-myc and c-jun, although initiation of all these events had already occurred after 1 h exposure to AN-9, the tumorigenicity of these cells tested in Balb/c mice was not affected. a marked reduction in the tumorigenicity of AN-9-treated cells was observed after 4 h of exposure. Exposure of the highly metastatic subclone of Lewis lung carcinoma (3LLD122) to AN-9 resulted in a very pronounced effect on the tumorigenicity of these cells tested in C57BL mice. Unlike WEHI cells, the tumorigenicity of 3LLD122 was almost completely diminished after 1 h of exposure. In both cell types a 10-fold higher concentration of BA did not affect the tumorigenicity of the cells as did AN-9.

Original languageEnglish
Pages (from-to)267-271
Number of pages5
JournalJournal of Cancer Research and Clinical Oncology
Volume123
Issue number5
DOIs
StatePublished - 1997

Keywords

  • Differentiation
  • Tumorigenicity
  • c-jun
  • c-myc

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