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The Antitumor Effect of Singlet Oxygen
1Institute of Virology, Medical Faculty, University Medical Center Freiburg, Freiburg, Germany georg.bauer@uniklinik-freiburg.de.
Abstract:
Tumor cells are protected against intercellular apoptosis-inducing signaling through expression of membrane-associated catalase and superoxide dismutase. Exogenous singlet oxygen derived from activated photosensitizers or from cold atmospheric plasma causes local inactivation of protective catalase which is followed by the generation of secondary extracellular singlet oxygen. This process is specific for tumor cells and is driven by a complex interaction between H2O2 and peroxynitrite. Secondary singlet oxygen has the potential for autoamplification of its generation, resulting in optimal inactivation of protective catalase and reactivation of intercellular apoptosis-inducing signaling. An increase in the endogenous NO concentration also causes inactivation of catalase and autoamplificatory generation of secondary singlet oxygen. This principle is essential for the antitumor activity of secondary plant products, such as cyanidins and other inhibitors of NO dioxygenase. It seems that the action of the established chemotherapeutic taxol and the recently established antitumor effect of certain azoles are based on the same principles.
Insights
Tumor cells evade apoptosis via protective enzymes. Singlet oxygen inactivates these enzymes, enabling cancer cell death and enhancing antitumor therapies like chemotherapy.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Tumor cells express membrane-associated catalase and superoxide dismutase, protecting them from apoptosis-inducing signals.
- Exogenous singlet oxygen can inactivate these protective enzymes, potentially re-sensitizing tumor cells.
Purpose of the Study:
- To elucidate the mechanism by which singlet oxygen induces tumor cell death.
- To explore the role of secondary singlet oxygen generation in antitumor activity.
- To investigate the connection between this mechanism and existing/novel cancer therapies.
Main Methods:
- Investigated the interaction between hydrogen peroxide (H2O2) and peroxynitrite in singlet oxygen generation.
- Studied the effect of endogenous nitric oxide (NO) concentration on catalase activity.
- Examined the antitumor activity of plant products (cyanidins) and azoles in relation to NO dioxygenase inhibition.
Main Results:
- Singlet oxygen generation is amplified by H2O2 and peroxynitrite, specifically targeting tumor cells.
- This process leads to catalase inactivation and restored apoptosis signaling.
- Increased endogenous NO concentration also triggers autoamplificatory singlet oxygen generation and catalase inactivation.
- Antitumor effects of cyanidins, taxol, and azoles appear to rely on this singlet oxygen-mediated mechanism.
Conclusions:
- Tumor cells' protective enzymes can be overcome by singlet oxygen, leading to apoptosis.
- Secondary singlet oxygen generation and its autoamplification are key to this antitumor effect.
- This mechanism underlies the efficacy of certain natural products and chemotherapeutics, offering new therapeutic avenues.
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