Chlorambucil-sensitive and -resistant lymphoid cells display different responses to the histone deacetylase inhibitor, sodium butyrate

Clinical chemoresistance is a frequent complication of alkylating agent treatment of malignant tumours. Chromatin remodelling using histone deacetylase inhibitors (e.g., sodium butyrate, NaBu) may increase target cell chemosensitivity. Apoptotic responses and expression of chromatin modifying enzymes in lymphoid cell lines, LP-1 and NCI-H929, to chlorambucil (CLB) and/or NaBu were examined in this study. NaBu augmented the apoptotic response in CLB-resistant LP-1 cells but antagonised it in CLB-sensitive NCI-H929 cells. CLB increased expression of methyltransferase I and histone acetyltransferase I in both cell lines while NaBu had only small effect. CLB-induced increased gene expression was attenuated by NaBu in CLB-sensitive NCI-H929 cells but not in resistant LP-1 cells. These results suggest that chromatin modifying agents may have differential effects on cells depending on their chemosensitivity.

Research highlights
► Sodium butyrate alters in vitro sensitivity of lymphoid cells to chlorambucil (CLB).
► CLB chemosensitivity is increased in resistant LP-1 cells.
► Butyrate antagonises CLB effect in sensitive NCI-H929 cells.
► CLB increases expression of chromatin modifying enzymes HAT1 and DNMT1.
► Butyrate attenuates CLB-induced HAT1 and DNMT1 expression more effectively in NCI-H929 cells.