Mitotic catastrophe induced in HeLa tumor cells by photodynamic therapy with methyl-aminolevulinate
Entity
UAM. Departamento de BiologíaPublisher
M D P I AGDate
2019-03-01Citation
10.3390/ijms20051229
International Journal of Molecular Sciences 20.5 (2019): 1229
ISSN
1422-0067 (online); 1661-6596 (print)DOI
10.3390/ijms20051229Funded by
This research was funded by Spanish grants from Instituto de Salud Carlos III MINECO and Feder Funds (FIS PI15/00974 and PI18/00708)Project
Gobierno de España. FIS PI15/00974; Gobierno de España. PI18/00708Editor's Version
https://doi.org/10.3390/ijms20051229Subjects
Cell death; HeLa tumor cells; Mitotic catastrophe; Photodynamic therapy; Spindle elements; Biología y Biomedicina / BiologíaRights
© 2019 by the authorsAbstract
Licensee MDPI, Basel, Switzerland. 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
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Google Scholar:Mascaraque Checa, Marta
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Delgado-Wicke, Pablo
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Damián, Alejandra
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Lucena, Silvia Rocío
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Carrasco, Elisa
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Juarranz de la Fuente, Ángeles
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