Different Functional States of Topoisomerase II can be Discriminated by Orthovanadate Sensitivity in Multi-drug Resistant Human Leukemic Cells

Abstract

We have studied the functional properties of topoisomerase II (Topo II) in a subclone of the HL-60 cell line, which is highly resistant to cytotoxic Topo II inhibitors, but does not express p-glycoprotein. The cells contain the two forms of human topo II with Mr 170 and 180 kDa in equal proportions. Two different states of both forms of the enzymes can be separated by anion-exchange chromatography and functionally discriminated on the basis of orthovanadate sensitivity. The EC₅₀ of orthovanadate was 0.2 μM for the early eluting and 30 μM for the late eluting Topo II.

Key Words:

• Orthovanadate
• topoisomerase II
• multidrug-resistance
• HI-60 cells