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 anti-tumour 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.