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 828 is not known, but recent results have indicated that induction of programmed 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 in human breast cancer cells in vitro. Both compounds were found to induce DNA fragmentation in the cells. However, microscopic examination of the cells demonstrated that CHS 828 and Taxol 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 no morphological characteristics of classical apoptosis were seen. In contrast, the cells in the Taxol-treated cultures displayed morphological features characteristic of classical apoptotic cells, but no Annexin-V positive cells could be observed. These findings together with the previously reported potent effects of CHS 828 on tumour cells, makes CHS 828 a promising new agent for the treatment of cancer patients.
Hansen
C M
CM
Department of Biochemistry, Leo Pharmaceutical Products, Industriparken 55, DK-2750 Ballerup Denmark. christina.hansen@leo-pharma.com
Hansen
D
D
Holm
P K
PK
Larsson
R
R
Binderup
L
L
D017304:Annexin A5 / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics; D003486:Cyanides / Q000494:pharmacology*; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D017304:Annexin A5; D000970:Antineoplastic Agents; D003486:Cyanides; D004273:DNA, Neoplasm; D006146:Guanidines; C401312:N-(6-chlorophenoxyhexyl)-N''-cyano-N''-4-pyridylguanidine; D009363:Neoplasm Proteins; D017239:Paclitaxel