Photodynamic therapy with TMPyP - Porphyrine induces mitotic catastrophe and microtubule disorganization in HeLa and G361 cells, a comprehensive view of the action of the photosensitizer

J Photochem Photobiol B. 2017 Aug:173:522-537. doi: 10.1016/j.jphotobiol.2017.06.029. Epub 2017 Jun 27.

Abstract

Photodynamic therapy (PDT) is a useful tool against cancer and various other diseases. PDT is capable to induce different cell death mechanisms, due to the PDT evoked reactive oxygen species (ROS) production and is dose dependent. It is known that cytoskeleton is responsible for numerous cell functions, including cell division, maintenance of cell shape, their adhesion ability and movement. PDT initiated redistribution and subsequent disintegration of cytoskeletal components that precedes cell death. Here was present our results in HeLa and G361 cells subjected to sublethal PDT treatments using α,β,χ,δ porphyrin-Tetrakis (1-methylpyridinium-4-yl) p-Toluenesulfonate porphyrin (TMPyP). The photosensitizer (PS) induced transient increasing of mitotic index (MI) observable early after PDT, cell cycle arrest, microtubule (MTs) disorganization of interphase cells, aberrant mitosis and formation of rounded cells with partial loss of adherence. Some cells were partly resistant to PDT induced MTs disorganization. The differences between both cell lines to PDT response were described. This is the first evidence of TMPyP - PDT induced microtubule disorganization and the cell death mechanisms known as mitotic catastrophe and the first detail analysis of microtubule aberrations of mitotic and interphase cells in HeLa and G361 cell lines. New modification of techniques of protein immunolabeling was developed.

Keywords: Aberrant mitosis; Cell cycle analysis; Fluorescent immunodetection; Multipolar spindle; PDT resistance.

MeSH terms

  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / radiation effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • HeLa Cells
  • Histones / metabolism
  • Humans
  • Light
  • Microscopy, Fluorescence
  • Microtubules / chemistry
  • Microtubules / metabolism*
  • Mitosis / drug effects*
  • Mitosis / radiation effects
  • Neoplasms / drug therapy
  • Photochemotherapy
  • Photosensitizing Agents / pharmacology*
  • Photosensitizing Agents / therapeutic use
  • Porphyrins / pharmacology*
  • Porphyrins / therapeutic use
  • Reactive Oxygen Species / metabolism

Substances

  • Histones
  • Photosensitizing Agents
  • Porphyrins
  • Reactive Oxygen Species
  • tetra(4-N-methylpyridyl)porphine