title: The nucleoside antagonist cordycepin causes DNA double strand breaks in breast cancer cells.
abstract: The fungal drug cordycepin (3-deoxyadenosine) is known to exert anti-tumor activities, preferentially by interfering with RNA synthesis. We have investigated the effect of cordycepin on human breast epithelial cell lines, ranging from non-malignant MCF10A cells to highly de-differentiated MDA-MB-435 cancer cells. Treatment of human breast cancer cells with cordycepin caused either apoptosis or persistent cell cycle arrest that was associated with reduced clonal growth of cordycepin-treated breast cancer cells. Highly de-differentiated breast cancer cell lines, such as MDA-MB-231 and MDA-MB-435, reacted more sensitive to cordycepin than less aggressive breast cancer cell lines (MCF7, T47D) or non-malignant breast epithelial cells (MCF10A), which poorly reacted to cordycepin. In cordycepin-sensitive breast cancer cells, a marked induction of the DNA damage response (DDR), including the phosphorylation of ATM, ATR, and histone γH2AX could be observed. These data indicate that cordycepin, which was believed to cause cancer cell death by inhibition of RNA synthesis, induces DNA double strand breaks in breast cancer cells. The genotoxic effect of cordycepin on breast cancer cells indicates a new mechanism of cordycepin-induced cancer cell death, and its activity against highly undifferentiated breast cancer cells provides a new perspective of how cordycepin may be used in the treatment of advanced breast cancer.
authors: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University Munich, Campus Grosshadern, Munich, Germany.
authors: Hong Jue
authors: HJ
authors: Lee
authors: Petra
authors: P
authors: Burger
authors: Marianne
authors: M
authors: Vogel
authors: Klaus
authors: K
authors: Friese
authors: Ansgar
authors: A
authors: Brüning
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000235:genetics; D003839:Deoxyadenosines / Q000494:pharmacology*; D005260:Female; D006657:Histones / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D009705:Nucleosides / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D012263:Ribonucleosides / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D003839:Deoxyadenosines; C468783:H2AX protein, human; D006657:Histones; D019384:Nucleic Acid Synthesis Inhibitors; D009705:Nucleosides; D011506:Proteins; D012263:Ribonucleosides; D025521:Tumor Suppressor Proteins; C024857:poly(ADP)-ribosylated proteins; D011064:Poly Adenosine Diphosphate Ribose; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C058120:cordycepin