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Cited by 77Photodynamic Therapy Research StudiesNanoplatforms for cancer theranosticsProtease and Inhibitor Mechanisms

Accelerated migration and invasion of prostate cancer cells after a photodynamic therapy-like challenge: Role of nitric oxide

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Fahey, Jonathan M., Girotti, Albert W.·2015·Nitric Oxide
DOI 10.1016/j.niox.2015.05.006PMC PMC4545398
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Abstract

Employing an in vitro model for 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT), we recently reported that human prostate cancer PC3 cells rapidly and persistently overexpressed inducible nitric oxide synthase (iNOS) and nitric oxide (NO) after a moderate ALA/light challenge. The upregulated iNOS/NO was shown to play a key role in cell resistance to apoptotic photokilling and also in the dramatic growth spurt observed in surviving cells. In the present study, we found that PC3 cells surviving an ALA/light insult not only proliferated faster than non-stressed controls, but migrated and invaded faster as well, these effects being abrogated by an iNOS inhibitor or NO scavenger. Photostressed prostate DU145 cells exhibited similar behavior. Using in-gel zymography, we showed that PC3 extracellular matrix metalloproteinase-9 (MMP-9) was strongly activated 24 h after ALA/light treatment and that MMP-9 inhibitor TIMP-1 was downregulated, consistent with MMP-9 involvement in enhanced invasiveness. We also observed a photostress-induced upregulation of α6 and β1 integrins, implying their involvement as well. The MMP-9, TIMP-1, and integrin effects were strongly attenuated by iNOS inhibition, confirming NO's role in photostress-enhanced migration/invasion. This study reveals novel, potentially tumor-promoting, side-effects of prostate cancer PDT which may be averted through use of iNOS inhibitors as PDT adjuvants.

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  • Increased NO production after low doses of ALA-PDT with less than ~25% cell killing not only prevented tumor cell death but also made surviving tumor cells more proliferative and migratory.

    “Such increased NO production, which occurred after low doses of ALA-PDT with less than ~25% cell killing, not only prevented tumor cell death but also made surviving tumor cells more proliferative and migratory [144,145,146].”

    From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [146]

    The Results sections report that stress-induced iNOS/NO increased resistance to photokilling and promoted proliferation and migration in surviving prostate cancer cells. However, the reported PC3 viable fraction was ~0.6 after 24 hours—about 40% cell killing, not less than ~25%. NO reduced cell death rather than preventing it entirely. (LLM, conf=0.88)

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References 47 · Cited by 77

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Authors
Fahey, J. M., & Girotti, A. W.
Affiliations
Medical College of Wisconsin (US)
Corresponding author
Girotti, Albert W.
ORCID
Venue
Nitric Oxide
Publisher
Elsevier BV
Published
2015-09
Volume
49
Pages
47-55
ISSN
1089-8603 (ISSN-L)
DOI
10.1016/j.niox.2015.05.006
PMC
PMC4545398
OpenAlex
W619017962
Cited by
77
References
47
Citations by year
2026: 2 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 9 · 2021: 6 · 2020: 11 · 2019: 10 · 2018: 5 · 2017: 8 · 2016: 7 · 2015: 1
FWCI
5.54
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Nitric Oxide (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • USPHS (CA70823)
  • MCW Cancer Center and Wisconsin Breast Cancer Showhouse for a Cure
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 › Cancer Research › Protease and Inhibitor Mechanisms
Keywords
prostate cancer, photodynamic therapy, 5-aminolevulinic acid, inducible nitric oxide synthase, cell migration, tumor invasion, MMP-9, TIMP-1, integrins, photostress, iNOS inhibitors, PC-3 cells, DU145 cells
MeSH terms
Cell Movement, Humans, Male, Neoplasm Invasiveness, Nitric Oxide, Photochemotherapy, Prostatic Neoplasms, Protoporphyrins, Up-Regulation, Photosensitizing Agents, Cell Line, Tumor, Nitric Oxide Synthase Type II

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