EFFECT OF ANTHRAQUINONE-LAXATIVES ON THE PROLIFERATION AND UROKINASE SECRETION OF NORMAL, PREMALIGNANT AND MALIGNANT COLONIC EPITHELIAL-CELLS

Even though 1,8-dihydroxyanthraquinone (DHA)-laxatives have been impli cated in colon carcinogenesis, the available information is still inco nclusive. The aim of this study was to demonstrate the effect of the D HA-laxatives, danthrone, rhein, aloe-emodin and sennidine, on colorect al tumour cells. In SW480 carcinoma cultures, dose-dependent induction of urokinase secretion into the medium was the predominant effect. Si multaneously, cell numbers were decreased by DHA-aglycones, but not by sennoside or the biphenylic laxative bisacodyl. DNA synthesis was not similarly reduced: 0.4-4 mu M danthrone and sennidine even stimulated 5-bromo-2'-desoxyuridine (BrdU) uptake into DNA. When uptake was norm alised to cell number, danthrone and sennidine doubled BrdU uptake/10( 6) cells, 18 mu M rhein and 0.7 mu M aloe-emodin induced increases of 37 and 50%, respectively. This may at least partially be due to select ive resistance of S-phase cells to DHA-caused cell loss. In VACO235 ad enoma cells, sennidine and aloe-emodin did not affect urokinase secret ion, but stimulated growth. Both cell numbers and DNA synthesis were i ncreased. In contrast to SW480 carcinoma cells, VACO235 cells were als o sensitive to sennoside and bisacodyl. No effects of DHA were observe d in normal colorectal epithelial cells. The biological effects were p receeded by specific phosphorylation of cellular proteins with molecul ar weights of 110, 78, 63, 57 kDa, indicating the specific induction o f a cellular signalling cascade by the laxatives. (C) 1998 Elsevier Sc ience Ltd. All rights reserved.