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Open AccessArticle

Mitotic Catastrophe Induced in HeLa Tumor Cells by Photodynamic Therapy with Methyl-aminolevulinate

1
Departamento de Biología, Universidad Autónoma de Madrid, 28049 Madrid, Spain
2
Instituto Ramón y Cajal de Investigaciones Sanitarias, IRYCIS, 28034 Madrid, Spain
3
Department of Basic Health Sciences, Faculty of Health Sciences, Rey Juan Carlos University, 28922 Alcorcón, Madrid, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(5), 1229; https://doi.org/10.3390/ijms20051229
Received: 1 February 2019 / Revised: 1 March 2019 / Accepted: 7 March 2019 / Published: 11 March 2019
(This article belongs to the Special Issue Cell Targets and Toxicity)
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. View Full-Text
Keywords: photodynamic therapy; HeLa tumor cells; cell death; mitotic catastrophe; spindle elements photodynamic therapy; HeLa tumor cells; cell death; mitotic catastrophe; spindle elements
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MDPI and ACS Style

Mascaraque, M.; Delgado-Wicke, P.; Damian, A.; Lucena, S.R.; Carrasco, E.; Juarranz, Á. Mitotic Catastrophe Induced in HeLa Tumor Cells by Photodynamic Therapy with Methyl-aminolevulinate. Int. J. Mol. Sci. 2019, 20, 1229.

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