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 implicated in colon carcinogenesis, the available information is still inconclusive. The aim of this study was to demonstrate the effect of the DHA-laxatives, danthrone, rhein, aloe-emodin and sennidine, on colorectal tumour cells. In SW480 carcinoma cultures, dose-dependent induction of urokinase secretion into the medium was the predominant effect. Simultaneously, 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 microM danthrone and sennidine even stimulated 5-bromo-2'-desoxyuridine (BrdU) uptake into DNA. When uptake was normalised to cell number, danthrone and sennidine doubled BrdU uptake/10(6) cells, 18 microM rhein and 0.7 microM aloe-emodin induced increases of 37 and 50%, respectively. This may at least partially be due to selective resistance of S-phase cells to DHA-caused cell loss. In VACO235 adenoma cells, sennidine and aloe-emodin did not affect urokinase secretion, but stimulated growth. Both cell numbers and DNA synthesis were increased. In contrast to SW480 carcinoma cells, VACO235 cells were also sensitive to sennoside and bisacodyl. No effects of DHA were observed in normal colorectal epithelial cells. The biological effects were preceeded by specific phosphorylation of cellular proteins with molecular weights of 110, 78, 63, 57 kDa, indicating the specific induction of a cellular signalling cascade by the laxatives.
Schörkhuber
M
M
Institute of Tumour Biology--Cancer Research, University of Vienna, Austria.
Richter
M
M
Dutter
A
A
Sontag
G
G
Marian
B
B
D000880:Anthraquinones / Q000009:adverse effects*; D002400:Cathartics / Q000009:adverse effects*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D000880:Anthraquinones; D002400:Cathartics; D014568:Urokinase-Type Plasminogen Activator