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Effects of ouabain on NIH/3T3 cells transformed with retrovirai oncogenes and on human tumor cell lines
Author(s) -
Tagliaferri Pierosandro,
Yanagihara Kazuyoshi,
Ciardiello Fortunate,
Talbot Neil,
Flatow Ursula,
Benade Leonard,
Bassin Robert H.
Publication year - 1987
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910400514
Subject(s) - ouabain , 3t3 cells , tumor cells , cell culture , human cell , cell , cancer research , medicine , chemistry , endocrinology , microbiology and biotechnology , biology , biochemistry , genetics , transfection , sodium , organic chemistry
Both murine and human cell lines transformed by the v‐Ki‐ ras gene have been shown to be much more sensitive to the toxic effects of the cardiac glycoside ouabain than their respective controls. This differential toxicity has previously been used in the isolation of flat revertant clones from populations of Kirsten murine sarcoma virus transformed NIH/3T3 cells. Here, we have undertaken a further characterization of this phenomenon in murine and human tumor cells. Two different techniques, a 51 Cr‐release assay and a quantitative Crystal violet elution assay, have been employed to compare the sensitivities to ouabain of normal and v‐Ki‐ ras ‐transformed NIH/3T3 cells. In each assay, ras ‐transformed NIH/3T3 cell lines displayed an increased sensitivity to ouabain as compared to the parental NIH/3T3 cell line, both in dose‐response and in time‐course experiments. In a separate study, ouabain was also able to inhibit the growth in semi‐solid medium of 2 v‐Ki‐ ras ‐transformed NIH/3T3 cell lines (DT and K‐NIH) in a dose‐dependent fashion. The same concentrations of ouabain were effective in both the 51 Cr‐release and Crystal violet assays. To address the question of whether increased sensitivity to ouabain is a specific result of transformation with the ras oncogene or is a common event which accompanies transformation by other oncogenes, we have screened a variety of transformed NIH/3T3 derivatives. All of these lines displayed an increased sensitivity to ouabain when compared to the parental NIH/3T3 cell line.