A cardiotonic steroid bufalin-like factor in human plasma induces leukemia cell differentiation.

Abstract

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.

• Authors: S Numazawa, Y Honma, T Yamamoto, T Yoshida, Y Kuroiwa
• Journal: Leukemia research (Leuk Res) Vol. 19 Issue 12 Pg. 945-53 (Dec 1995) ISSN: 0145-2126 [Print] England
• PMID: 8632664 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biological Factors
• Bufanolides
• Cardiotonic Agents
• Enzyme Inhibitors
• Sodium-Potassium-Exchanging ATPase
• bufalin

Topics

• Antineoplastic Agents (blood, isolation & purification, pharmacology)
• Biological Factors (blood, isolation & purification, pharmacology)
• Bufanolides (blood, isolation & purification, pharmacology)
• Cardiotonic Agents (blood, isolation & purification, pharmacology)
• Cell Differentiation (drug effects)
• Chemical Fractionation
• Chromatography, High Pressure Liquid
• Enzyme Inhibitors (blood, isolation & purification, pharmacology)
• Humans
• Leukemia (pathology)
• Sodium-Potassium-Exchanging ATPase (antagonists & inhibitors)
• Tumor Cells, Cultured (drug effects, pathology)