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Cited by 26Photodynamic Therapy Research StudiesNitric Oxide and Endothelin EffectsNanoplatforms for cancer theranostics

Upregulation of pro-tumor nitric oxide by anti-tumor photodynamic therapy

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Girotti, Albert W., Fahey, Jonathan M.·2020·Biochemical Pharmacology
DOI 10.1016/j.bcp.2019.113750PMC PMC7263973
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Abstract

Many malignant tumors use endogenous nitric oxide (NO) to promote survival, growth, and metastatic migration. This NO, which is typically generated by inducible nitric oxide synthase (iNOS), can also antagonize various anti-cancer therapies and its source is most often assumed to be constitutive or pre-existing iNOS. In this paper, we provide evidence (i) that many different cancer cells exhibit resistance to oxidative killing by photodynamic therapy (PDT), and (ii) that cells surviving the challenge grow, migrate and invade more aggressively, as do non-targeted bystander cells. Accompanying these effects are activation or upregulation of pro-survival/progression effector proteins such as NF-κB, Akt, and Survivin. Observed in the author's laboratory, these responses were not attributed to basal iNOS/NO in most cases, but rather to NO from enzyme that was strongly upregulated by photodynamic stress. Each of these effects and how they can be mitigated by inhibitors of iNOS activity or transcription, or by NO scavengers will be discussed. When approved for clinical use, such pharmacologic agents could improve PDT efficacy as well as reduce potentially negative side-effects of this therapy.

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Authors
Girotti, A. W., & Fahey, J. M.
Affiliations
Medical College of Wisconsin (US)
Corresponding author
Girotti, Albert W.
ORCID
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
2020-06
Volume
176
Pages
113750
ISSN
0006-2952 (ISSN-L)
DOI
10.1016/j.bcp.2019.113750
PMC
PMC7263973
OpenAlex
W2995833799
Cited by
26
References
56
Citations by year
2026: 1 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 7
FWCI
0.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochemical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
Office of Extramural Research, National Institutes of Health
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
Keywords
nitric oxide, photodynamic therapy, inducible nitric oxide synthase, oxidative stress resistance, tumor cell migration and invasion, NF-κB, Akt, survivin, bystander cells, NO scavenger, iNOS inhibitors, tumor progression
MeSH terms
Animals, Cell Survival, Humans, Neoplasms, Nitric Oxide, Photochemotherapy, Transcriptional Activation, Up-Regulation, Apoptosis, Nitric Oxide Synthase Type II

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