Abstract
A novel butyric acid derivative, pivaloyloxymethyl butyrate, AN-9, was previously shown to be a potent differentiating agent. AN-9 exerts a significant anticancer activity in vitro and in vivo. In all the activities examined, AN-9 was more potent than butyric acid. Here we show that AN-9 and butyric acid induce cell death by apoptosis. Exposure of HL-60 cells to butyric acid and AN-9 decreased cell numbers and induced cell differentiation and the appearance of typical apoptotic features. Induction of apoptosis and/or differentiation by AN-9 and butyric acid was dependent on the concentration and the time of exposure to the drugs. The advantage of AN-9 over butyric acid was further confirmed. Apoptosis induced by AN-9 occurred after a shorter exposure and at lower drug concentrations than that induced by butyric acid. Apoptosis by AN-9 was accompanied by reduction in Bcl-2 expression. Preincubation with antioxidants did not protect HL-60 cells from apoptosis induced by AN-9. HL-60 cells that were induced to differentiate by preincubation with retinoic acid or low AN-9 concentrations were more resistant to apoptosis, induced later by high concentrations of AN-9, than were undifferentiated cells.
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Abbreviations
- AN-9:
-
pivaloyloxymethylbutyrate
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This work is part of the Ph.D. thesis of Yael Zimra of the Sackler School of Medicine, Tel Aviv University
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Zimra, Y., Wasserman, L., Maron, L. et al. Butyric acid and pivaloyloxymethyl butyrate, AN-9, a novel butyric acid derivative, induce apoptosis in HL-60 cells. J Cancer Res Clin Oncol 123, 152–160 (1997). https://doi.org/10.1007/BF01214667
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DOI: https://doi.org/10.1007/BF01214667