Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy

Nat Med. 2011 Jul 3;17(7):860-6. doi: 10.1038/nm.2385.


In cancer treatment, apoptosis is a well-recognized cell death mechanism through which cytotoxic agents kill tumor cells. Here we report that dying tumor cells use the apoptotic process to generate potent growth-stimulating signals to stimulate the repopulation of tumors undergoing radiotherapy. Furthermore, activated caspase 3, a key executioner in apoptosis, is involved in the growth stimulation. One downstream effector that caspase 3 regulates is prostaglandin E(2) (PGE(2)), which can potently stimulate growth of surviving tumor cells. Deficiency of caspase 3 either in tumor cells or in tumor stroma caused substantial tumor sensitivity to radiotherapy in xenograft or mouse tumors. In human subjects with cancer, higher amounts of activated caspase 3 in tumor tissues are correlated with markedly increased rate of recurrence and death. We propose the existence of a cell death-induced tumor repopulation pathway in which caspase 3 has a major role.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Caspase 3 / metabolism
  • Caspase 3 / physiology*
  • Cell Death / physiology
  • Cell Death / radiation effects
  • Cell Line, Tumor
  • Cell Proliferation
  • Dinoprostone / metabolism
  • Dinoprostone / physiology
  • Group VI Phospholipases A2 / metabolism
  • Humans
  • Mice
  • Neoplasms, Experimental / radiotherapy*


  • Group VI Phospholipases A2
  • Pla2g6 protein, mouse
  • Caspase 3
  • Dinoprostone