Potential suitability of Na+/K (+) -transporting ATPase in pre-screens for anti-cancer agents
Repke, K.R.; Schön, R.; Megges, R.; Weiland, J.; Nissen, E.; Matthes, E.
Anti-Cancer Drug Design 10(2): 177-187
1995
ISSN/ISBN: 0266-9536 PMID: 7710638 Document Number: 451342
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 K-0.5 values for the inhibition of EMAC Na/K-ATPase display the expected dependence on steroid structure, the IC-50 values for the suppression of EMAC cell proliferation all lie within a narrow concentration range. With ouabain, the IC-50 value for the suppression of proliferation of oestrogen receptor-negative, human mammary carcinoma (MCA) cells is four orders of magnitude higher than the K-0.5 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.