Regulated necrosis in HeLa cells induced by ZnPc photodynamic treatment: a new nuclear morphology

Int J Mol Sci. 2014 Dec 9;15(12):22772-85. doi: 10.3390/ijms151222772.

Abstract

Photodynamic therapy (PDT) is a cancer treatment modality based on the administration of a photosensitizer (PS), which accumulates preferentially in tumor cells. Subsequent irradiation of the neoplastic area triggers a cascade of photochemical reactions that leads to the formation of highly reactive oxygen species responsible for cell inactivation. Photodynamic treatments in vitro are performed with the PS, zinc-phthalocyanine (ZnPc). The PS is near the plasma membrane during uptake and internalization. Inactivation clearly occurs by a necrotic process, manifested by nuclear pyknosis, negative TUNEL and Annexin V assays and non-relocation of cytochrome c. In contrast, by increasing the incubation time, ZnPc is accumulated in the Golgi apparatus and produces cell inactivation with characteristics of apoptosis and necrosis: TUNEL positive, relocated cytochrome c and negative Annexin V assay. This type of death produces a still undescribed granulated nuclear morphology, which is different from that of necrosis or apoptosis. This morphology is inhibited by necrostatin-1, a specific inhibitor of regulated necrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Cell Death / drug effects
  • Cell Death / radiation effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / pathology
  • Cell Nucleus / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Dose-Response Relationship, Drug
  • HeLa Cells
  • Humans
  • Imidazoles / pharmacology
  • Indoles / metabolism
  • Indoles / pharmacology*
  • Isoindoles
  • Necrosis / etiology*
  • Necrosis / pathology*
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacology*
  • Photochemotherapy
  • Photosensitizing Agents / metabolism
  • Photosensitizing Agents / pharmacology*
  • Zinc Compounds

Substances

  • Imidazoles
  • Indoles
  • Isoindoles
  • Organometallic Compounds
  • Photosensitizing Agents
  • Zinc Compounds
  • necrostatin-1
  • Zn(II)-phthalocyanine