Photolon™ - Photosensitization induces apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes

Mohamed Ali-Seyed, Ramaswamy Bhuvaneswari, Khee Chee Soo, Malini Olivo

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The localization of photosensitizers in the subcellular compartments during photodynamic therapy (PDT) plays a major role in the cell destruction; therefore, the aim of this study was to investigate the intracellular localization of Chlorin e6-PVP (Photolon™) in malignant and normal cells. Our study involves the characterization of the structural determinants of subcellular localization of Photolon, and how subcellular local- ization affects the selective toxicity of Photolon towards tumor cells. Using confocal laser scanning microscopy (CLSM) and fluorescent organelle probes; we examined the subcellular localization of Photolon™ in the murine colon carcinoma CT-26 and normal fibroblast (NHLC) cells. Our results demonstrated that after 30 min of incubation, the distribution of Photolon was localized mainly in the cytoplasmic organelles including the mitochondria, lysosomes, Golgi apparatus, around the nuclear envelope and also in the nucleus but not in the endoplasmic reticulum whereas in NHLC cells, Photolon was found to be localized minimally only in the nucleus not in other organelles studied. The relationship between subcellular local- ization of Photolon and PDT-induced apoptosis was investigated. Apoptotic cell death was judged by the formation of known apoptotic hallmarks including, the phosphatidylserine external- ization (PS), PARP cleavage, a substrate for caspase-3 and the formation of apoptotic nuclei. At the irradiation dose of 1 J/cm2, the percentage of apoptotic cells was 80%, respectively. This study provided substantial evidence that Photolon preferentially localized in the subcellular organelles in the following order: nucleus, mitochondria, lysosomes and the Golgi apparatus and subsequent photodamage of the mitochondria and lysosomes played an important role in PDT-mediated apoptosis CT-26 cells. Our results based on the cytoplasmic organelles and the intranuclear localization extensively enhance the efficacy of PDT with appropriate photosensitizer and light dose and support the idea that PDT can contribute to elimination of malignant cells by inducing apoptosis, which is of physiological significance.

Original languageEnglish
Pages (from-to)821-831
Number of pages11
JournalInternational Journal of Oncology
Volume39
Issue number4
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

Fingerprint

Photosensitivity Disorders
Lysosomes
Mitochondria
Apoptosis
Photochemotherapy
Organelles
Photosensitizing Agents
Golgi Apparatus
Photolon
Phosphatidylserines
Nuclear Envelope
Fluorescent Dyes
Confocal Microscopy
Caspase 3
Endoplasmic Reticulum
Colon
Cell Death
Fibroblasts
Carcinoma
Light

Keywords

  • Apoptosis
  • Lysosomes
  • Mitochondria
  • Photolon™
  • Photosensitization

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Photolon™ - Photosensitization induces apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes. / Ali-Seyed, Mohamed; Bhuvaneswari, Ramaswamy; Soo, Khee Chee; Olivo, Malini.

In: International Journal of Oncology, Vol. 39, No. 4, 10.2011, p. 821-831.

Research output: Contribution to journalArticle

Ali-Seyed, Mohamed ; Bhuvaneswari, Ramaswamy ; Soo, Khee Chee ; Olivo, Malini. / Photolon™ - Photosensitization induces apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes. In: International Journal of Oncology. 2011 ; Vol. 39, No. 4. pp. 821-831.
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