title: Cordycepin induces cell cycle arrest and apoptosis by inducing DNA damage and up-regulation of p53 in Leukemia cells.
abstract: Cordycepin, an adenosine analog derived from Cordyceps militaris has been shown to exert anti-tumor activity in many ways. However, the mechanisms by which cordycepin contributes to the anti-tumor still obscure. Here our present work showed that cordycepin inhibits cell growth in NB-4 and U937 cells by inducing apoptosis. Further study showed that cordycepin increases the expression of p53 which promotes the release of cytochrome c from mitochondria to the cytosol. The released cytochrome c can then activate caspase-9 and trigger intrinsic apoptosis. Cordycepin also blocks MAPK pathway by inhibiting the phosphorylation of ERK1/2, and thus sensitizes the apoptosis. In addition, our results showed that cordycepin inhibits the expression of cyclin A2, cyclin E, and CDK2, which leads to the accumulation of cells in S-phase. Moreover, our study showed that cordycepin induces DNA damage and causes degradation of Cdc25A, suggesting that cordycepin-induced S-phase arrest involves activation of Chk2-Cdc25A pathway. In conclusion, cordycepin-induced DNA damage initiates cell cycle arrest and apoptosis which leads to the growth inhibition of NB-4 and U937 cells.
authors.affiliation: a Key Laboratory of Systems Biomedicine (Ministry of Education); Shanghai Center for Systems Biomedicine ; Shanghai Jiao Tong University ; Shanghai , China.
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Liao
authors.forename: Jianya
authors.initials: J
authors.lastname: Ling
authors.forename: Guoying
authors.initials: G
authors.lastname: Zhang
authors.forename: Fengjun
authors.initials: F
authors.lastname: Liu
authors.forename: Shengce
authors.initials: S
authors.lastname: Tao
authors.forename: Zeguang
authors.initials: Z
authors.lastname: Han
authors.forename: Saijuan
authors.initials: S
authors.lastname: Chen
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.forename: Huangying
authors.initials: H
authors.lastname: Le
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D004249:DNA Damage; D003839:Deoxyadenosines / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008954:Models, Biological; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D003839:Deoxyadenosines; D016159:Tumor Suppressor Protein p53; D020169:Caspases; C058120:cordycepin
keywords: ATM, Ataxia telangiectasia mutated; ATR, ATM and Rad3-related; Cdc25A; DNA damage; PFT-α, Pifithrin-α; PI, Propidium iodide; S-phase arrest; XIAP, X-linked inhibitor of apoptosis protein.; apoptosis; cordycepin; cytochrome c; p53