Cyanoguanidine CHS 828 induces programmed cell death with apoptotic features in human breast cancer cells in vitro

The cyanoguanidine CHS 828 was recently shown to possess potent anti-tumour effects both in vitro and in vivo. The exact mechanism of action of CHS 82 8 is not known, but recent results have indicated that induction of program med cell death may be one mechanism by which CHS 828 exerts its anti-tumour effects. To investigate this aspect in more detail, we studied the effect of CHS 828 and the reference compound Taxol beta on programmed cell death i n human breast cancer cells in vitro. Both compounds were found to induce D NA fragmentation in the cells. However; microscopic examination of the cell s demonstrated that CHS 828 and Taxol(R) triggered different types of cell death. In the CHS 828-treated cultures most cells were found to be Annexin- V positive, indicating that these cells were early apoptotic cells, while n o morphological characteristics of classical apoptosis were seen. In contra st, the cells in the Taxol(R)-treated cultures displayed morphological feat ures characteristic of classical apoptotic cells, but no Annexin-V positive cells could be observed. These findings together with the previously repor ted potent effects of CHS 828 on tumour cells, makes CHS 828 a promising ne w agent for the treatment of cancer patients.