Induction of senescence by adenosine suppressing the growth of lung cancer cells

Biochem Biophys Res Commun. 2013 Oct 11;440(1):62-7. doi: 10.1016/j.bbrc.2013.09.030. Epub 2013 Sep 17.

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: A549 cell; Adenosine; Cellular senescence; DNA damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / pharmacology
  • Adenosine / therapeutic use*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cellular Senescence / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Female
  • Humans
  • Lung / drug effects*
  • Lung / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antineoplastic Agents
  • Cyclin-Dependent Kinase Inhibitor p21
  • Tumor Suppressor Protein p53
  • Adenosine