Catalase protects tumor cells from apoptosis induction by intercellular ROS signaling.
Transformed cells are subject to intercellular induction of apoptosis by neighbouring nontransformed cells and to autocrine apoptotic self-destruction. Both processes depend on extracellular superoxide anion generation by the transformed cells and on the release of peroxidase from both nontransformed and transformed cells. This concerted action results in HOCl synthesis, HOCl-superoxide anion interaction and generation of apoptosis-inducing hydroxyl radicals. In contrast to transformed cells, ex vivo tumor cells are resistant against intercellular induction of apoptosis and autocrine apoptotic self-destruction. Resistance of tumor cells against intercellular ROS signaling depends on interference through catalase expression on the membrane. Intercellular ROS signaling of tumor cells can be restored when i) exogenous HOCl is added; ii) exogenous hydrogen peroxide is supplied, or iii) catalase is inhibited. These findings define the biochemical basis for specific apoptosis induction in tumor cells through re-establishment of intercellular ROS signaling, a potential novel approach in tumor prevention and therapy.
Bechtel
Wibke
W
Harvard Medical School, BIDMC, Departmentof Matrix Biology, Boston, MA 02215, USA.
Bauer
Georg
G
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002374:Catalase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000494:pharmacology; D051379:Mice; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D017382:Reactive Oxygen Species; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D002374:Catalase