O(2/3) exposure inhibits cell progression affecting cyclin B1/cdk1 activity in SK-N-SH while induces apoptosis in SK-N-DZ neuroblastoma cells

J Cell Physiol. 2007 Oct;213(1):115-25. doi: 10.1002/jcp.21097.


In search for innovative therapeutic agents for children neuroblastoma, the oxygen therapy could be considered an alternative anti-tumoral treatment. Given the physiochemical properties of O(2/3) gas mixture including fairly low aqueous solubility and spreading, and the interesting perspective of hyperoxia, we analyzed the inhibitory effect of O(2/3) treatment on two human neuroblastoma cell lines (SK-N-SH and SK-N-DZ). In this study, we demonstrated that O(2/3) treatment was able to induce cell growth inhibition and cell cycle perturbation in both cell lines. We observed an arrest at G(2) phase, accompanied by an alteration in the expression and localization of cyclin B1/cdk1 complex and a reduction in its activity in SK-N-SH cells. This reduction was consistent with the increase in both Wee1 and chk1 protein levels. On the contrary, O(2/3) induced apoptosis in SK-N-DZ cells via caspase 3 activation and Poly ADP-ribose polymerase-1 (PARP) cleavage, associated with an increase in the pro-apoptotic Bax protein. Consequently, we considered the possibility of improving the responsiveness to chemotherapeutic agents such as Cisplatin, Etoposide, and Gemcitabine in combination with O(2/3) treatment. The combined treatments produced a stronger cell inhibitory effect than Cisplatin and Etoposide used alone in SK-N-SH cells. On the contrary, the combination data were not significantly different from O(2/3) treatment alone in SK-N-DZ cells, thus suggesting that the obtained changes in cell growth inhibition were due to the effect of O(2/3) alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • CDC2 Protein Kinase / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Cyclin B / metabolism
  • Cyclin B1
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Etoposide / pharmacology
  • Gemcitabine
  • Humans
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology*
  • Oxygen / pharmacology*
  • Ozone / pharmacology*
  • Reactive Oxygen Species / metabolism


  • Antineoplastic Agents
  • CCNB1 protein, human
  • Cyclin B
  • Cyclin B1
  • Reactive Oxygen Species
  • Deoxycytidine
  • Ozone
  • Etoposide
  • CDC2 Protein Kinase
  • Cisplatin
  • Oxygen
  • Gemcitabine