Ant 4,4, a polyamine-anthracene conjugate, induces cell death and recovery in human promyelogenous leukemia cells (HL-60)

Rui Traquete, Radiah Abdul Ghani, Otto Phanstiel, Heather M. Wallace

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

One of the major problems in cancer therapy is the lack of specificity of chemotherapeutic agents towards cancer cells, resulting in adverse side effects. One means to counter this is to selectively deliver the drug to the cancer cell. Cancer cells accumulate increased concentrations of polyamines compared to normal cells, mainly through an increased uptake of preformed polyamines via the polyamine transport system (PTS). Furthermore, the non-stringent structural requirements of the PTS enable the transport of a range of polyamine-based molecules. Thus the PTS can be used to transport compounds linked to polyamines selectively to cancer cells. In our laboratory, polyamine-anthracene conjugates have shown potent antitumour activity towards HL-60 cells. The aim of this study was to determine the cytotoxicity of Ant-4,4, a homospermidine-anthracene conjugate, and assess the long term effects by determining whether cancer cells were able to recover from treatment. During exposure, Ant-4,4 was an effective growth-inhibitory agent in HL-60 cells decreasing viable cell number, protein and polyamine content. Evidence indicates concomitant cell cycle arrest and increased apoptosis. Once the drug was removed, HL-60 cells recovered gradually over time. Increasing cell number, protein content and polyamine content, as well as diminished effects on cell-cycle and apoptotic stimuli were observed over time. These data suggest that, despite being an effective way of delivering anthracene, these polyamine conjugates do not exert long-lasting effects on HL-60 cells.
Original languageEnglish
Pages (from-to)1193-1203
Number of pages10
JournalAmino Acids
Volume44
Issue number4
Early online date6 Jan 2013
DOIs
Publication statusPublished - Apr 2013

Keywords

  • cancer
  • recovery of cancer cells
  • polyamine conjugate
  • targeted drug delivery

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