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).
Plasma membrane-associated 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 less than 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 less than 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.
Hirano
T
T
Division of Clinical Pharmacology, Tokyo College of Pharmacy, Tokyo, Japan.
Fukuoka
K
K
Oka
K
K
Matsumoto
Y
Y
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000328:Adult; D000368:Aged; D001593:Benzyl Compounds / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000201:enzymology*
D001593:Benzyl Compounds; C063012:2,3-dibenzylbutane-1,4-diol; D000251:Adenosine Triphosphatases