Version 1
: Received: 23 April 2023 / Approved: 24 April 2023 / Online: 24 April 2023 (04:26:43 CEST)
How to cite:
Girotti, A. W.; Bazak, J.; Korytowski, W. Pro-tumor Bystander Effects of Nitric Oxide in Anti-tumor Photodynamic Therapy. Preprints2023, 2023040819. https://doi.org/10.20944/preprints202304.0819.v1
Girotti, A. W.; Bazak, J.; Korytowski, W. Pro-tumor Bystander Effects of Nitric Oxide in Anti-tumor Photodynamic Therapy. Preprints 2023, 2023040819. https://doi.org/10.20944/preprints202304.0819.v1
Girotti, A. W.; Bazak, J.; Korytowski, W. Pro-tumor Bystander Effects of Nitric Oxide in Anti-tumor Photodynamic Therapy. Preprints2023, 2023040819. https://doi.org/10.20944/preprints202304.0819.v1
APA Style
Girotti, A. W., Bazak, J., & Korytowski, W. (2023). Pro-tumor Bystander Effects of Nitric Oxide in Anti-tumor Photodynamic Therapy. Preprints. https://doi.org/10.20944/preprints202304.0819.v1
Chicago/Turabian Style
Girotti, A. W., Jerzy Bazak and Witold Korytowski. 2023 "Pro-tumor Bystander Effects of Nitric Oxide in Anti-tumor Photodynamic Therapy" Preprints. https://doi.org/10.20944/preprints202304.0819.v1
Abstract
Recent studies have revealed that several cancer cell types can upregulate inducible nitric oxide synthase (iNOS) and iNOS-derived nitric oxide (NO) after a moderate photodynamic challenge sensitized by 5-aminolevulinic acid (ALA)-induced protoporphyrin-IX. The NO signaled for cell resistance to photokilling as well as greater growth and migration/invasion aggressiveness of surviving cells. On this basis, it was predicted that diffusible NO from PDT-targeted cells in a tumor might enhance growth, migration, and invasiveness of non- or poorly PDT-targeted bystander cells. This was tested using a novel approach in which ALA-PDT targeted cancer cells on a culture dish were initially segregated from non-targeted bystander cells of the same type via impermeable silicone-rimmed rings. Several hours after LED irradiation, the rings were removed, and both cell populations analyzed in the dark for various responses. After a moderate extent of targeted cell killing (~25%), bystander proliferation and migration were evaluated, and both were found to be significantly enhanced. Enhancement corelated with iNOS/NO upregulation in surviving PDT-targeted cancer cells in the following cell type order: PC3 > MDA-MB-231 >U87 > BLM. If occurring in an actual PDT-challenged tumor, such bystander effects might compromise treatment efficacy by stimulating tumor growth and/or metastatic dissemination. Possible mitigation of these negative effects by using pharmacologic inhibitors of iNOS expression or activity as PDT adjuvants will be discussed.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
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