Differential Sensitivity of Human Gastric Cancer ATPase and Normal Gastric Mucosa ATPase to the Synthetic Mammalian Lignan Analogue 2,3-Dibenzylbutane-1,4-diol (Hattalin)

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Abstract
Plasma membrane-associàted adenosine triphosphatase (ATPase) samples partially purified from the tumor dissections of 15 gastric cancer patients were examined for sensitivity to the synthetic lignan, 2,3-dibenzylbutane-1,4-diol (hattalin), and ouabain in the presence of Mg2+, Na+, and K+. Hattalin was the strongest Na+, K+-ATPase inhibitor among the lignans previously examined. The enzyme from normal gastric tissue of the same patient was used as control. The specific activity of ATPase from cancer tissue (C-ATPase) was inhibited by more than 50% by 2.0 mM hattalin, whereas only 33.1% of the specific activity of ATPase from normal gastric mucosa (N-ATPase) was inhibited by 2.0 mM hattalin. There was statistical significance of lignan sensitivity between C- and N-ATPase (p < 0.02). Ouabain also inhibited C-ATPase in preference to N-ATPase, though not significantly. Hattalin inhibited both C- and N-ATPase more strongly than did ouabain (p < 0.05). Moreover, the lignan inhibited both C- and N-ATPase in the absence of Na+ and K+. From these data, it is evident that the sensitivity of plasma membrane-associated to lignan increased by gastric canceration. The target ATPase of hattalin is likely to be one other than sodium- and potassium-dependent, ouabain-sensitive ATPase.