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Cited by 84Photodynamic Therapy Research StudiesNanoplatforms for cancer theranosticsCell death mechanisms and regulation

Cytoprotective induction of nitric oxide synthase in a cellular model of 5-aminolevulinic acid-based photodynamic therapy

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Bhowmick, Reshma, Girotti, Albert W.·2010·Free Radical Biology and Medicine
DOI 10.1016/j.freeradbiomed.2010.01.040PMC PMC2856718
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Abstract

Photodynamic therapy (PDT) employs a photosensitizing agent, molecular oxygen, and visible light to generate reactive species that kill tumor and tumor vasculature cells. Nitric oxide produced by these cells could be procarcinogenic by inhibiting apoptosis or promoting angiogenesis and tumor growth. The purpose of this study was to determine whether tumor cells upregulate NO as a cytoprotective measure during PDT. Breast tumor COH-BR1 cells sensitized in their mitochondria with 5-aminolevulinic acid (ALA)-derived protoporphyrin IX died apoptotically after irradiation, ALA- and light-only controls showing no effect. Western analysis revealed that inducible nitric oxide synthase (iNOS) was upregulated >3-fold within 4 h after ALA/light treatment, whereas other NOS isoforms were unaffected. Exposing cells to a NOS inhibitor (L-NAME or 1400W) during photochallenge enhanced caspase-3/7 activation and apoptotic killing up to 2- to 3-fold while substantially reducing chemiluminescence-assessed NO production, suggesting that this NO was cytoprotective. Consistently, the NO scavenger cPTIO enhanced ALA/light-induced caspase-3/7 activation and apoptotic kill by >2.5-fold. Of added significance, cells could be rescued from 1400W-exacerbated apoptosis by an exogenous NO donor, spermine-NONOate. This is the first reported evidence for increased tumor cell resistance due to iNOS upregulation in a PDT model. Our findings indicate that stress-elicited NO in PDT-treated tumors could compromise therapeutic efficacy and suggest NOS-based pharmacologic interventions for preventing this.

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  • Reducing NO production by either a NOS inhibitor or a NO scavenger enhanced PDT-induced apoptosis, whereas increasing NO level by an exogenous NO donor prevented such enhanced apoptosis, suggesting that NO induced by ALA-PDT protects tumor cells from PDT-induced cell death.

    “Reducing NO production by either a NOS inhibitor or a NO scavenger enhanced PDT-induced apoptosis, whereas increasing NO level by an exogenous NO donor prevented such enhanced apoptosis, suggesting that NO induced by ALA-PDT protects tumor cells from PDT-induced cell death.”

    From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [142]

  • PDT upregulates the level of iNOS (but not other isoforms of NOS) by several folds within hours after treatment in COH-BR1 human breast cancer cell line.

    “PDT was shown to upregulate the level of iNOS (but not other isoforms of NOS) by several folds within hours after treatment in COH-BR1 human breast cancer cell line [142].”

    From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [142]

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Authors
Bhowmick, R., & Girotti, A. W.
Affiliations
Medical College of Wisconsin (US)
Corresponding author
Girotti, Albert W.
ORCID
Girotti, Albert W.
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2010-05
Volume
48
Issue
10
Pages
1296-1301
ISSN
0891-5849 (ISSN-L)
DOI
10.1016/j.freeradbiomed.2010.01.040
PMC
PMC2856718
OpenAlex
W1982800230
Cited by
84
References
3
Citations by year
2025: 1 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 14 · 2020: 6 · 2019: 9 · 2018: 3 · 2017: 3 · 2016: 8 · 2015: 10 · 2014: 3 · 2013: 7 · 2012: 4
FWCI
4.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Hope Center for Neurological Disorders
  • U.S. Public Health Service
  • National Cancer Institute (CA70823, R01CA070823)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
photodynamic therapy, 5-aminolevulinic acid, inducible nitric oxide synthase, nitric oxide, cytoprotection, apoptosis, caspase-3/7 activation, protoporphyrin IX, breast tumor cells, L-NAME, 1400W, cPTIO, spermine NONOate, tumor resistance, nitric oxide synthase inhibitors
MeSH terms
Adenocarcinoma, Aminolevulinic Acid, Breast Neoplasms, Enzyme Activation, Epithelial Cells, Female, Humans, Light, Photochemotherapy, Apoptosis, Nitric Oxide Synthase, NG-Nitroarginine Methyl Ester, Cytoprotection, Caspases, Cell Line, Tumor

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