A cardiotonic steroid bufalin-like factor in human plasma induces leukemia cell differentiation.
A Na+,K(+)-ATPase inhibitor, bufalin, has been shown previously to induce leukemia cell differentiation. The presence of a circulating Na+,K(+)-ATPase inhibitor has been proposed in mammals. The aim of this study was to explore an endogenous bufalin-like factor that induces leukemia cell differentiation. We found a fraction, designated as fraction A, obtained from human plasma extract that inhibits the growth of several human-derived leukemia cell lines. The effect of the fraction was retained after protease digestion or heat treatment. Murine leukemia cells and ouabain-resistant cells, which are insensitive to bufalin, appeared to be refractory to fraction A in terms of growth inhibition. Fraction A also induced functional and morphological maturation in THP-1 cells. Fraction A was recognized by anti-bufalin anti-serum and inhibited 3H-bufalin binding to K562 cells. These findings suggest that fraction A shows a similar behavior to that of bufalin on leukemia cells by inhibiting Na+,K(+)-ATPase. We propose that an endogenous Na+,K(+)-ATPase inhibitor in human plasma may play a role in cell differentiation.
Numazawa
S
S
Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Honma
Y
Y
Yamamoto
T
T
Yoshida
T
T
Kuroiwa
Y
Y
D000970:Antineoplastic Agents / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D001685:Biological Factors / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D002018:Bufanolides / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D005591:Chemical Fractionation; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D001685:Biological Factors; D002018:Bufanolides; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D000254:Sodium-Potassium-Exchanging ATPase; C022777:bufalin