Elsevier

Leukemia Research

Volume 19, Issue 12, December 1995, Pages 945-953
Leukemia Research

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

https://doi.org/10.1016/0145-2126(95)00081-XGet rights and content

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.

References (30)

  • J.M. Hamlyn et al.

    A circulating inhibitor of (Na+ + K+)ATPase associated with essential hypertension

    Nature

    (1982)
  • L. Poston et al.

    Evidence for a circulating sodium transport inhibitor in essential hypertension

    Br. Med. J.

    (1981)
  • F.J. Haddy

    Endogenous digitalis-like factor or factors

    New Engl. J. Med.

    (1987)
  • A. Goto et al.

    Physiology and pharmacology of endogenous digitalis-like factors

    Pharmacol. Rev.

    (1992)
  • S. Vasdev et al.

    Dehydroepiandrosterone sulfate as a digitalis like factor in plasma of healthy human adults

    Res. Commun. Chem. Path. Pharmacol.

    (1985)
  • Cited by (23)

    • Cardenolides from the Apocynaceae family and their anticancer activity

      2016, Fitoterapia
      Citation Excerpt :

      UNBS-1450, a semisynthetic derivative of the natural cardenolide UNBS1244 (isolated from the African plant Calotropis procera), can block cell proliferation in four different human non-small cell lung carcinomas (A549, NCI-H727, A427, and CAL-12T) at nanomolar concentrations, and has also entered phase I clinical trial in Belgium [10–12]. More than that, several studies have revealed the effective dose of cardenolides on inducing apoptosis in human tumor cells with no significant toxicity on normal cells [13–15]. Many of the plants from Apocynaceae family are known to contain cardenolides, mainly distributing in the genera of Nerium, Thevetia, Cerbera, Apocynum and Strophanthus.

    View all citing articles on Scopus
    View full text