Water induces autocrine stimulation of tumor cell killing through ATP release and P2 receptor binding

N. Selzner, M. Selzner, R. Graf, U. Ungethuem, J. G. Fitz, P. A. Clavien

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Although exposure of cells to extreme hypotonic stress appears to be a purely experimental set up, it has found an application in clinical routine. For years, surgeons have washed the abdominal cavity with distilled water to lyse isolated cancer cells left after surgery. No data are available supporting this practice or evaluating the potential mechanisms of cell injury under these circumstances. Recent evidence indicates that increases in cell volume stimulate release of adenosine triphosphate and autocrine stimulation of purinergic (P2) receptors in the plasma membrane of certain epithelial cell types. Under physiological conditions, purigenic stimulation can contribute to cell volume recovery through activation of solute efflux. In addition, adenosine triphosphate-P2 receptor binding might trigger other mechanisms affecting cell viability after profound hypotonic stress. This study demonstrates a novel pathway of cell death by apoptosis in human colon cancer cells following a short hypotonic stress. This pathway is induced by transitory cell swelling which leads to extracellular release of adenosine triphosphate (ATP) and specific binding of ATP to P2 receptors (probably P2X7). Extracellular ATP induced activation of caspases 3 and 8, annexin V, release of cytochrome c, and eventually cell death. The effect of ATP can be blocked by addition of (I) apyrase to hydrolyse extracellular ATP and (ii) suramin, a P2 receptor antagonist. Finally, (iii) gadolinium pretreatment, a blocker of ATP release, reduces sensitivity of the cells to hypotonic stress. The adenosine triphosphate-P2 receptor cell death pathway suggests that autocrine/paracrine signaling may contribute to regulation of viability in certain cancer cells disclosed with this pathway.

Original languageEnglish (US)
JournalCell Death and Differentiation
Volume11
Issue numberSUPPL. 2
DOIs
StatePublished - Dec 2004

Fingerprint

Adenosine Triphosphate
Water
Osmotic Pressure
Neoplasms
Cell Death
Cell Size
Autocrine Communication
Paracrine Communication
Purinergic P2X7 Receptors
Apyrase
Purinergic P2 Receptors
Suramin
Abdominal Cavity
Caspase 8
Annexin A5
Gadolinium
Cytochromes c
Caspase 3
Colonic Neoplasms
Cell Survival

Keywords

  • Apoptosis
  • ATP
  • Colon cancer cells
  • P2 receptor

ASJC Scopus subject areas

  • Cell Biology

Cite this

Water induces autocrine stimulation of tumor cell killing through ATP release and P2 receptor binding. / Selzner, N.; Selzner, M.; Graf, R.; Ungethuem, U.; Fitz, J. G.; Clavien, P. A.

In: Cell Death and Differentiation, Vol. 11, No. SUPPL. 2, 12.2004.

Research output: Contribution to journalArticle

Selzner, N. ; Selzner, M. ; Graf, R. ; Ungethuem, U. ; Fitz, J. G. ; Clavien, P. A. / Water induces autocrine stimulation of tumor cell killing through ATP release and P2 receptor binding. In: Cell Death and Differentiation. 2004 ; Vol. 11, No. SUPPL. 2.
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