Effects of sodium butyrate, dimethylsulfoxide and dibutyryl cAMP on the poorly differentiated ovarian adenocarcinoma cell line AMOC-2.
To determine whether the poorly differentiated AMOC-2 human ovarian adenocarcinoma cell line was capable of undergoing differentiation, AMOC-2 cells were exposed to 2 mM sodium butyrate, 2.5% dimethylsulfoxide, or 4 mM dibutyryl cyclic adenosine monophosphate (dibutyryl cAMP) for 6 days. These treatments resulted in growth inhibition, a reduction in clonogenicity and an increase in cellular glycogen content. Significant increases in heat stable alkaline phosphatase activity also occurred after exposure to sodium butyrate. In addition, a thorn-like microfilament structure observed in untreated cells was diminished concomitantly with morphological changes that included flattening, enlargement and extended cytoplasmic processes after exposure to sodium butyrate or dibutyryl cAMP. Furthermore, treatment with sodium butyrate increased the intracellular concentrations of beta-tubulin, vimentin, neurofilaments (M(r) 210,000) and cytokeratin (M(r) 56,000-58,000). These changes were completely reversed after removal of the inducing agent. The findings suggest that treatment of AMOC-2 cells with sodium butyrate induced a more differentiated phenotype, although terminal differentiation was not achieved.
Yabushita
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Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
Sartorelli
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D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000469:Alkaline Phosphatase / Q000032:analysis / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005455:Fluorescent Antibody Technique; D006003:Glycogen / Q000032:analysis; D006801:Humans; D015151:Immunoblotting; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D002087:Butyrates; D003598:Cytoskeletal Proteins; D020148:Butyric Acid; D003994:Bucladesine; D006003:Glycogen; D000469:Alkaline Phosphatase; D004121:Dimethyl Sulfoxide