tretinoin and Rectal-Neoplasms

The effect of sodium butyrate and retinoic acid added singly or in combination on substrate-dependent growth, colonization efficiency in soft agar, and carcino-embryonic antigen (CEA) production in three human colorectal carcinoma cell lines differing in their degree of differentiation was studied. All three colon cancer cell lines regardless of their state of differentiation had their growth markedly slowed by sodium butyrate, and to a lesser extent by retinoic acid. When both agents were added together, a small synergistic inhibition of growth was noted in all the cell lines. Butyrate eliminated colony formation in soft agar in all three cell lines, however, retinoic acid only reduced colony formation in the well differentiated cell line DLD-2. Sodium butyrate was able to induce CEA production in the undifferentiated cell (MIP-101) and the moderately differentiated cells (clone D) which were previously negative for this marker. It also enhanced the baseline production of CEA in the well differentiated cells (DLD-2). Retinoic acid did not induce CEA production in clone D or MIP-101 cells, but did enhance the production of CEA in DLD-2 cells. When both retinoic acid and sodium butyrate were added together, CEA production was either additive (DLD-2) or was inhibited (clone D and MIP-101). One explanation of these results is that only well differentiated cells have functional cellular retinoic acid-binding protein (cRABP), and that certain actions of retinoic acid (inhibition of anchorage-dependent growth) are independent of the presence of cRABP.

Topics: Butyrates; Butyric Acid; Carcinoembryonic Antigen; Cell Adhesion; Cell Division; Cell Line; Colonic Neoplasms; Humans; Rectal Neoplasms; Tretinoin

In the present study, we have examined the neutral glycolipids, gangliosides, and sulfoglycolipids of human rectal adenocarcinoma (HRT-18) cells and the alterations produced by the differentiating agents, sodium butyrate, dimethyl sulfoxide, and retinoic acid. Thin-layer chromatography of neutral glycolipids showed that HRT-18 cells contained mono- and diglycosylceramides. Cells treated with differentiating agents had additional glycolipids which comigrated with tri- and tetraglycosylceramides. Labeling of neutral glycolipids with [3H]galactose showed that HRT-18 cells also contain glycosylceramides larger than diglycosylceramides which also were altered by treatment with differentiating agents. In studies of acidic glycolipids, GM3, the major ganglioside in untreated cells, was reduced in cells treated with retinoic acid but not in cells treated with other agents. Upon labeling with radioactive galactose, changes were seen only in the minor ganglioside components of treated cells. Differentiating agents also altered the patterns of sulfogalactolipids and fucolipids in HRT-18 cells. In the case of fucolipids, 2 new bands were observed in the cells treated with dimethyl sulfoxide and retinoic acid. The changes brought about by differentiating agents may identify glycolipids involved in the process of tumorigenicity.

Topics: Adenocarcinoma; Butyrates; Butyric Acid; Cell Line; Chromatography, Thin Layer; Dimethyl Sulfoxide; Fucose; Galactose; Gangliosides; Glycolipids; Humans; Rectal Neoplasms; Tretinoin; Tritium

The effects of sodium butyrate, dimethyl sulfoxide (DMSO), and retinoic acid on the growth, morphology, carcinoembryonic antigen content, cell surface membrane-associated enzyme activities, and glycoprotein profiles of a human rectal adenocarcinoma cell line (HRT-18) in culture were compared. All three agents reversibly caused a marked increase in doubling times, a decrease in saturation densities, and a markedly reduced colony-forming efficiency in soft agar. Only butyrate caused gross morphological changes including cell enlargement, flattening, and increased membranous process formation. Carcinoembryonic antigen content was increased during culture in butyrate, while it was reduced by DMSO and unchanged by retinoic acid. The activities of membrane-associated enzymes were altered significantly in the butyrate-treated cells. For example, an increase in the activities of alkaline phosphatase (10-fold), gamma-glutamyl transpeptidase activity (3-fold) and sucrase activity (2-fold) was observed, while those of aminooligopeptidase and K+-stimulated phosphatase actually showed slight decreases. DMSO- or retinoic acid-treated cells showed a marked decrease in alkaline phosphatase activity, but other enzyme activities remained unchanged. Surface protein-labeling patterns of lactoperoxidase-catalyzed iodinated HRT-18 cells showed no significant change from the control cells following treatment with DMSO or retinoic acid. The most prominent change caused by butyrate treatment was the appearance of a major glycoprotein band with an apparent molecular weight of 60,000. These data indicate that the use of butyrate, DMSO, and retinoic acid may provide useful information concerning the identification of differentiation-associated markers of human rectal cancer cells. Furthermore, these agents, although having similar effects on the growth properties, have different effects on the morphology and on the biochemical properties of human rectal cancer cells.

Topics: Adenocarcinoma; Antigens, Neoplasm; Antigens, Surface; Butyrates; Butyric Acid; Cell Division; Cell Line; Cell Membrane; Dimethyl Sulfoxide; Electrophoresis, Polyacrylamide Gel; Glycoproteins; Humans; Neoplasm Proteins; Rectal Neoplasms; Tretinoin