Bcl-2 expression regulates sodium butyrate-induced apoptosis in human MCF-7 breast cancer cells.
Sodium butyrate (butyrate) is a potent growth inhibitor and differentiating agent for many cell types, including breast cancer cells. Programmed cell death, or apoptosis, is a physiological mechanism of cell death that is dependent on both preexisting proteins and de novo protein synthesis. In the studies presented here, we investigated the role of apoptosis in the growth regulation of human MCF-7 breast cancer cells by sodium butyrate. We report that butyrate treatment of breast cancer MCF-7 cells causes a nonreversible growth inhibition by inducing apoptosis in a time- and dose-dependent manner. Treatment of MCF-7 cells for as little as 12 h with butyrate caused a 5.6-fold induction in apoptotic cell death, which continued to increase up to 27-fold by 48 h treatment. The butyrate-induced apoptosis in MCF-7 cells was closely linked with the down-regulation of expression of Bcl-2 mRNA and Bcl-2 protein, a gene product known to be involved in the regulation of apoptosis in mammalian cells. The observed relationship between the down-regulation of Bcl-2 and induction of apoptosis was not causal because stable overexpression of Bcl-2 resulted in protection of MCF-7 cells from the cytotoxic morphological changes and growth-inhibitory effects of butyrate (15% growth inhibition compared to 60% growth inhibition in the parental cells). In addition, Bcl-2-overexpressing MCF-7 cells exhibited a significant suppression in butyrate-induced stimulation of apoptosis (5-fold increase in apoptosis compared to 27-fold in parental MCF-7 cells). These findings demonstrate that the levels of Bcl-2 expression regulate the butyrate-induced apoptosis in breast cancer cells and that butyrate may potentially be useful in sensitizing the breast cancer cells to chemotherapy-induced apoptosis.
Mandal
M
M
Department of Medicine, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Kumar
R
R
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002087:Butyrates / Q000494:pharmacology* / Q000633:toxicity; D020148:Butyric Acid; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D002087:Butyrates; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D020148:Butyric Acid