Thioredoxin-1 inhibitor PX-12 induces human acute myeloid leukemia cell apoptosis and enhances the sensitivity of cells to arsenic trioxide

Int J Clin Exp Pathol. 2014 Jul 15;7(8):4765-73. eCollection 2014.

Abstract

Thioredoxin-1 (Trx-1), an important redox regulatory factor, plays a significant role in drug-induced apoptosis. Here we investigated the effects of the Trx-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) on human acute myeloid leukemia cells (AML) and the sensitivity of cells to arsenic trioxide (As2O3, ATO). Treatment of cells with a different concentration of PX-12 for 48 h resulted in growth inhibition, the induction of apoptosis and increased the levels of activated caspase-3 expression in AML cell lines HL-60, NB4, U937 and primary AML cells in a dose-dependent manner. In addition, PX-12 enhanced the sensitivity of U937 cells to ATO. These results suggest the effects of Trx-1 inhibitor PX-12 to induce apoptosis in AML cells and therapeutic potential in AML by enhancing the sensitivity of cells to ATO.

Keywords: PX-12; acute myeloid leukemia; apoptosis; arsenic trioxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Arsenic Trioxide
  • Arsenicals / pharmacology
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Disulfides / pharmacology*
  • Flow Cytometry
  • HL-60 Cells
  • Humans
  • Imidazoles / pharmacology*
  • Leukemia, Myeloid, Acute*
  • Oxides / pharmacology
  • Thioredoxins / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Arsenicals
  • Disulfides
  • Imidazoles
  • Oxides
  • TXN protein, human
  • Thioredoxins
  • 1-methylpropyl-2-imidazolyl disulfide
  • Arsenic Trioxide