The effect of each of twelve mammalian
lignan derivatives on the growth of human mammary
tumor ZR-75-1 cells was examined. At a concentration less than 10 micrograms/ml,
tumor cell growth was inhibited from 18-68%. The effect of 2,3-dibenzylbutane-1,4-diol(hattalin) was found to be strongest, inhibiting growth by 50% at a concentration (EC50) of 2.1 micrograms/ml.
Hattalin inhibited membrane Na+, K(+)-
ATPase of canine kidney cortex. It also inhibited the
ATPase of the plasma membrane fraction from both cultured cells and a section of human
breast cancer tissue at a concentration ranging from 0.5 to 2.0 mM. However, only a few percent of membrane
ATPase from either ZR-75-1 cells or
breast carcinoma tissue was inhibited by 2.0 mM of
ouabain, suggesting that the target
ATPase of
hattalin was other than
ouabain-sensitive
ATPase. The relative incorporation of [3H]
thymidine per 1 x 10(5) cells into the
acid-precipitable fraction of ZR-75-1 cells was not affected by 1-50 micrograms/ml of
hattalin, while a marked decrease resulted from 1-10 micrograms/ml of
5-fluorouracil (5-FU). These results suggest that the suppressive effect of
hattalin on
tumor cell growth may not occur through inhibition of
DNA synthesis but rather partly by inhibition of the plasma membrane
ATPase other than Na+ and K(+)-dependent ones.