Bystander effect in photosensitized prostate cancer cells with a different grade of malignancy: The role of nitric oxide

Nitric Oxide. 2022 Nov 1:128:25-36. doi: 10.1016/j.niox.2022.08.002. Epub 2022 Aug 12.

Abstract

Photodynamic therapy (PDT) is a therapeutic modality based on the simultaneous action of three elements: photosensitizer, light and oxygen. This triad generates singlet oxygen and reactive oxygen species that can reduce the mass of a tumor. PDT is also able to stimulate iNOS, the enzyme that generates nitric oxide (NO). The role of NO in PDT-treated cancer cells has been investigated in several studies. They showed that low iNOS/NO levels stimulate signaling pathways that promote tumor survival, while high iNOS/NO levels arrest tumor growth. There is increasing evidence that ROS/RNS control both proliferation and migration of cells in the vicinity of PDT-treated tumor cells (so-called bystander cells). In this work, we addressed the question of how NO, which is generated by weak PDT, affects bystander cells. We used a conditioned medium: medium of PDT-treated tumor cells containing the stressors produced by the cells was added to untreated cells mimicking the neighboring bystander cells to investigate whether the conditioned medium affects cell proliferation. We found that low-level NO in prostate cancer cells affects the bystander tumor cells in a manner that depends on their malignancy grade.

Keywords: Bystander effect; GSNOR; Nitric oxide; Photodynamic therapy; Prostate cancer cells; S-nitrosylation; Tumor malignancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bystander Effect
  • Cell Line, Tumor
  • Cell Survival
  • Culture Media, Conditioned / pharmacology
  • Humans
  • Male
  • Nitric Oxide / metabolism
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Prostatic Neoplasms* / drug therapy
  • Reactive Oxygen Species / metabolism

Substances

  • Culture Media, Conditioned
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • Nitric Oxide