title: Cordycepin-induced apoptosis and autophagy in breast cancer cells are independent of the estrogen receptor.
abstract: Cordycepin (3-deoxyadenosine), found in Cordyceps spp., has been known to have many therapeutic effects including immunomodulatory, anti-inflammatory, antimicrobial, and anti-aging effects. Moreover, anti-tumor and anti-metastatic effects of cordycepin have been reported, but the mechanism causing cancer cell death is poorly characterized. The present study was designed to investigate whether the mechanisms of cordycepin-induced cell death were associated with estrogen receptor in breast cancer cells. Exposure of both MDA-MB-231 and MCF-7 human breast cancer cells to cordycepin resulted in dose-responsive inhibition of cell growth and reduction in cell viability. The cordycepin-induced cell death in MDA-MB-231 cells was associated with several specific features of the mitochondria-mediated apoptotic pathway, which was confirmed by DNA fragmentation, TUNEL, and biochemical assays. Cordycepin also caused a dose-dependent increase in mitochondrial translocation of Bax, triggering cytosolic release of cytochrome c and activation of caspases-9 and -3. Interestingly, MCF-7 cells showed autophagy-associated cell death, as observed by the detection of an autophagosome-specific protein and large membranous vacuole ultrastructure morphology in the cytoplasm. Cordycepin-induced autophagic cell death has applications in treating MCF-7 cells with apoptotic defects, irrespective of the ER response. Although autophagy has a survival function in tumorigenesis of some cancer cells, autophagy may be important for cordycepin-induced MCF-7 cell death. In conclusion, the results of our study demonstrate that cordycepin effectively kills MDA-MB-231 and MCF-7 human breast cancer cell lines in culture. Hence, further studies should be conducted to determine whether cordycepin will be a clinically useful, ER-independent, chemotherapeutic agent for human breast cancer.
authors.affiliation: Department of Physiology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Sunga
authors.initials: S
authors.lastname: Choi
authors.forename: Mi-Hee
authors.initials: MH
authors.lastname: Lim
authors.forename: Ki Mo
authors.initials: KM
authors.lastname: Kim
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Jeon
authors.forename: Won O
authors.initials: WO
authors.lastname: Song
authors.forename: Tae Woong
authors.initials: TW
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D003839:Deoxyadenosines / Q000494:pharmacology* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000502:physiology*
chemical_list: D003839:Deoxyadenosines; D011960:Receptors, Estrogen; C058120:cordycepin