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Induction of senescence by adenosine suppressing the growth of lung cancer cells
Authors:Dongqin Yang  Junyao Song  Lijun Wu  Yunfang Ma  Chunhua Song  Sinisa Dovat  Tomoyuki Nishizaki  Jie Liu
Affiliation:1. Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China;2. Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;3. Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA;4. Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan
Abstract:Extracellular adenosine is well reported to suppress tumor growth by induction of apoptosis. However, in this study we found that adenosine treatment results in cellular senescence in A549 lung cancer cells both in vitro and in vivo; adenosine induces cell cycle arrest and senescence in a p53/p21 dependent manner; adenosine elevates the level of phosphor-γH2AX, pCHK2 and pBRCA1, the markers for prolonged DNA damage response which are likely responsible for initiating the cellular senescence. Our study first demonstrates that adenosine suppresses growth of cancer cells by inducing senescence and provides additional evidence that adenosine could act as an effective anticancer agent for targeted cancer therapy.
Keywords:Adenosine   Cellular senescence   A549 cell   DNA damage
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