Abstract

Photodynamic therapy (PDT) constitutes a cancer treatment modality based on the administration of a photosensitizer, which accumulates in tumor cells. The subsequent irradiation of the tumoral area triggers the formation of reactive oxygen species responsible for cancer cell death. One of the compounds approved in clinical practice is methyl-aminolevulinate (MAL), a protoporphyrin IX (PpIX) precursor intermediate of heme synthesis. We have identified the mitotic catastrophe (MC) process after MAL-PDT in HeLa human carcinoma cells. The fluorescence microscopy revealed that PpIX was located mainly at plasma membrane and lysosomes of HeLa cells, although some fluorescence was also detected at endoplasmic reticulum and Golgi apparatus. Cell blockage at metaphase-anaphase transition was observed 24 h after PDT by phase contrast microscopy and flow cytometry. Mitotic apparatus components evaluation by immunofluorescence and Western blot indicated: multipolar spindles and disorganized chromosomes in the equatorial plate accompanied with dispersion of centromeres and alterations in aurora kinase proteins. The mitotic blockage induced by MAL-PDT resembled that induced by two compounds used in chemotherapy, taxol and nocodazole, both targeting microtubules. The alterations in tumoral cells provided evidence of MC induced by MAL-PDT, resolving mainly by apoptosis, directly or through the formation of multinucleate cells.

Highlights

  • Photodynamic therapy (PDT) is a minimally invasive treatment modality

  • There are the 5-aminolevulinic acid (ALA) and its ester derivatives, such as the methyl-aminolevulinate (MAL). Both are prodrugs commonly used in the clinical practice that are enzymatically turned into Protoporphyrin IX (PpIX), a potent PS [11]

  • Cell viability of HaCaT cells, used as non-tumorigenic control cells, after the same treatments was always higher than 80%, which supports the selectivity of the treatment

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Summary

Introduction

Photodynamic therapy (PDT) is a minimally invasive treatment modality Still emerging, it is already a successful therapeutic procedure used for the management of oncologic and non-oncologic diseases [1,2]. None of them are individually toxic, but their combination triggers the photodynamic reaction which is tumor ablative by generating highly reactive oxygen species (ROS), mainly singlet oxygen (1O2) [6]. These molecules have short half-life and a destruction radius in the range of nanometers, being, the main targets the organelles where PSs are located [7,8]. Both are prodrugs commonly used in the clinical practice that are enzymatically turned into Protoporphyrin IX (PpIX), a potent PS [11]

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