Antileukemic activity of an arsenomolybdate in the human HL-60 and U937 leukemia cells

J Inorg Biochem. 2017 Mar:168:67-75. doi: 10.1016/j.jinorgbio.2016.12.002. Epub 2016 Dec 16.

Abstract

The antileukemic activity, mechanisms and serum albumin interactions of an arsenomolybdate, K2Na[AsMo6O21(O2CCH2NH3)3]·6H2O (1), was evaluated in the human leukemia HL-60 and U937 cells. The results indicated that 1 could inhibit the proliferation of both leukemia cell lines in a dose-dependent manner with the 50% lethal concentration (IC50) value of 8.61μM for HL-60 and 14.50μM for U937 at 24h, compare to the positive controls, all-trans retinoic acid (ATRA) with IC50 value of 20.76μM and 14.85μM,and As2O3 with IC50 value of 6.40μM and 8.75μM at 24h, respectively (P<0.05). Furthermore, the anti-leukemia activity of compound 1 might be medicated by arresting the leukemic cells in the G1 phase and inducing apoptosis via caspase-3 and bcl-2 regulatory proteins. Spectroscopic techniques results showed that the fluorescence of human serum albumin was quenched by compound 1, and the quenching mechanism was mainly static quenching. Compound 1 might be a potential medicinal candidate against acute promyelocytic leukemia.

Keywords: Acute promyelocytic leukemia; Apoptosis; Arsenomolybdate; Polyoxometalates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Arsenicals / chemical synthesis
  • Arsenicals / chemistry
  • Arsenicals / pharmacology*
  • Blotting, Western
  • Caspase 3 / drug effects*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Drug Stability
  • Flow Cytometry
  • Fluorescence
  • HL-60 Cells
  • Humans
  • Inhibitory Concentration 50
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Molybdenum / chemistry
  • Molybdenum / pharmacology*
  • U937 Cells

Substances

  • Antineoplastic Agents
  • Arsenicals
  • Molybdenum
  • Caspase 3