Hexadecylphosphocholine causes rapid cell death in canine mammary tumour cells.
Hexadecylphosphocholine (HePC, Miltefosine) is an antitumour phospholipid and known inducer of apoptosis in human breast cancer cells. The mechanism underlying the induction of cell death by HePC, however, is not clear yet. In this study, we have investigated the cytotoxic effects of HePC on canine mammary tumour cells (CMTs) in vitro. Upon addition of HePC, CMTs rapidly exhibited several features that resembled apoptotic cell death. Cells showed externalization of phosphatidylserine, a hallmark of apoptosis, within 5 min after addition of HePC at concentrations as low as 10 microM. Furthermore, rapid swelling of mitochondria was observed. Rounding and detachment of cells followed within 30 min. However, fragmentation of nuclear DNA could not be observed. Overall, HePC was shown to induce a type of cell death in CMTs that in some aspects resembles apoptosis, though the process proceeds much more rapidly than reported for other tumour cell lines.
Department of Biochemistry and Cell biology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584 CM, Utrecht, The Netherlands.
Daniël
D
Duijsings
Martin
M
Houweling
Arie B
AB
Vaandrager
Jan A
JA
Mol
Katja J
KJ
Teerds
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D006224:Cricetinae; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000473:pathology*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D010767:Phosphorylcholine; C039128:miltefosine