title: Potential suitability of Na+/K(+)-transporting ATPase in pre-screens for anti-cancer agents.
abstract: Twenty-five compounds [digitalis (generic name for cardenolides, bufadienolides and their glycosides) representatives and derivatives, various steroids as well as some customary carcinostatics] have been compared in terms of their potency to suppress the proliferation of Ehrlich mouse ascites carcinoma (EMAC) cells and to inhibit the activity of Na/K-ATPase from EMAC cells and from human cardiac muscle. The inhibitor susceptibilities of the Na/K-ATPase isoforms of EMAC and cardiac muscle are very different, in favour of the cardiac muscle with the digitalis-like acting steroids, whereas they are quite similar with the digitalis-unlike acting compounds. Whereas the K0.5 values for the inhibition of EMAC Na/K-ATPase display the expected dependence on steroid structure, the IC50 values for the suppression of EMAC cell proliferation all lie within a narrow concentration range. With ouabain, the IC50 value for the suppression of proliferation of oestrogen receptor-negative, human mammary carcinoma (MCA) cells is four orders of magnitude higher than the K0.5 value for inhibition of the activity of human cardiac muscle Na/K-ATPase. In contrast to this effectivity order, some synthetic derivatives of digitalis steroids develop primarily antiproliferative potency.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
authors.forename: K R
authors.initials: KR
authors.lastname: Repke
authors.forename: R
authors.initials: R
authors.lastname: Schön
authors.forename: R
authors.initials: R
authors.lastname: Megges
authors.forename: J
authors.initials: J
authors.lastname: Weiland
authors.forename: E
authors.initials: E
authors.lastname: Nissen
authors.forename: E
authors.initials: E
authors.lastname: Matthes
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006168:Guinea Pigs; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008546:Melanoma, Experimental / Q000201:enzymology / Q000473:pathology; D051379:Mice; D009206:Myocardium / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007527:Isoenzymes; D000254:Sodium-Potassium-Exchanging ATPase