ANTIPROLIFERATIVE EFFECTS OF SODIUM-BUTYRATE IN ADRIAMYCIN-SENSITIVE AND ADRIAMYCIN-RESISTANT HUMAN CANCER CELL-LINES

The proliferation of the MCF7 and MCF7-A (adriamycin-resistant) and KB -3-1 and KB-A (adriamycin-resistant) cell lines was arrested by sodium butyrate (NaBut) at 1 mM or higher concentrations. In the MCF7 and MC F7-A cell lines, an accumulation in the G(1) phase was observed, where as the KB-3-1 and KB-A cell lines accumulated in both G(1) and G(2)/M phases. The level of the mRNA coded by the 'early G(1)' gene c-myc was high in all these cell lines, and was only transiently decreased by N aBut treatment. The 'late' mRNA coding for the proliferating cell nucl ear antigen (PCNA) was also strongly expressed in all the cell lines s tudied; incubation with NaBut caused a decrease of the PCNA mRNA in th e MCF7 and MCF7-A cells but not in the KB-3-1 and KB-A cells. The anti -oncoprotein p(105)RB was undetectable in the MCF7 and MCF7-A cells, w hile the KB-3-1 as well as KB-A cells contained a high level of this p rotein. Neither the content nor the apparent state of phosphorylation of the RB protein were affected by incubation (up to 48 h) with NaBut.