Enhanced efficiency of cell death by lysosome-specific photodamage

Abstract Mobilization of specific mechanisms of regulated cell death is a promising alternative to treat challenging illness such as neurodegenerative disease and cancer. The use of light to activate these mechanisms may provide a route for target-specific therapies. Two asymmetric porphyrins with o...

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Autores principales:	Tayana Mazin Tsubone, Waleska Kerllen Martins, Christiane Pavani, Helena Couto Junqueira, Rosangela Itri, Maurício S. Baptista
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6765cd99e428408c839d3f769ecfba26
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spelling	oai:doaj.org-article:6765cd99e428408c839d3f769ecfba262021-12-02T15:05:28ZEnhanced efficiency of cell death by lysosome-specific photodamage10.1038/s41598-017-06788-72045-2322https://doaj.org/article/6765cd99e428408c839d3f769ecfba262017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06788-7https://doaj.org/toc/2045-2322Abstract Mobilization of specific mechanisms of regulated cell death is a promising alternative to treat challenging illness such as neurodegenerative disease and cancer. The use of light to activate these mechanisms may provide a route for target-specific therapies. Two asymmetric porphyrins with opposite charges, the negatively charged TPPS2a and the positively charged CisDiMPyP were compared in terms of their properties in membrane mimics and in cells. CisDiMPyP interacts to a larger extent with model membranes and with cells than TPPS2a, due to a favorable electrostatic interaction. CisDiMPyP is also more effective than TPPS2a in damaging membranes. Surprisingly, TPPS2a is more efficient in causing photoinduced cell death. The lethal concentration on cell viability of 50% (LC50) found for TPPS2a was ~3.5 (raw data) and ~5 (considering photosensitizer incorporation) times smaller than for CisDiMPyP. CisDiMPyP damaged mainly mitochondria and triggered short-term phototoxicity by necro-apoptotic cell death. Photoexcitation of TPPS2a promotes mainly lysosomal damage leading to autophagy-associated cell death. Our data shows that an exact damage in lysosome is more effective to diminish proliferation of HeLa cells than a similar damage in mitochondria. Precisely targeting organelles and specifically triggering regulated cell death mechanisms shall help in the development of new organelle-target therapies.Tayana Mazin TsuboneWaleska Kerllen MartinsChristiane PavaniHelena Couto JunqueiraRosangela ItriMaurício S. BaptistaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-19 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tayana Mazin Tsubone Waleska Kerllen Martins Christiane Pavani Helena Couto Junqueira Rosangela Itri Maurício S. Baptista Enhanced efficiency of cell death by lysosome-specific photodamage
description	Abstract Mobilization of specific mechanisms of regulated cell death is a promising alternative to treat challenging illness such as neurodegenerative disease and cancer. The use of light to activate these mechanisms may provide a route for target-specific therapies. Two asymmetric porphyrins with opposite charges, the negatively charged TPPS2a and the positively charged CisDiMPyP were compared in terms of their properties in membrane mimics and in cells. CisDiMPyP interacts to a larger extent with model membranes and with cells than TPPS2a, due to a favorable electrostatic interaction. CisDiMPyP is also more effective than TPPS2a in damaging membranes. Surprisingly, TPPS2a is more efficient in causing photoinduced cell death. The lethal concentration on cell viability of 50% (LC50) found for TPPS2a was ~3.5 (raw data) and ~5 (considering photosensitizer incorporation) times smaller than for CisDiMPyP. CisDiMPyP damaged mainly mitochondria and triggered short-term phototoxicity by necro-apoptotic cell death. Photoexcitation of TPPS2a promotes mainly lysosomal damage leading to autophagy-associated cell death. Our data shows that an exact damage in lysosome is more effective to diminish proliferation of HeLa cells than a similar damage in mitochondria. Precisely targeting organelles and specifically triggering regulated cell death mechanisms shall help in the development of new organelle-target therapies.
format	article
author	Tayana Mazin Tsubone Waleska Kerllen Martins Christiane Pavani Helena Couto Junqueira Rosangela Itri Maurício S. Baptista
author_facet	Tayana Mazin Tsubone Waleska Kerllen Martins Christiane Pavani Helena Couto Junqueira Rosangela Itri Maurício S. Baptista
author_sort	Tayana Mazin Tsubone
title	Enhanced efficiency of cell death by lysosome-specific photodamage
title_short	Enhanced efficiency of cell death by lysosome-specific photodamage
title_full	Enhanced efficiency of cell death by lysosome-specific photodamage
title_fullStr	Enhanced efficiency of cell death by lysosome-specific photodamage
title_full_unstemmed	Enhanced efficiency of cell death by lysosome-specific photodamage
title_sort	enhanced efficiency of cell death by lysosome-specific photodamage
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6765cd99e428408c839d3f769ecfba26
work_keys_str_mv	AT tayanamazintsubone enhancedefficiencyofcelldeathbylysosomespecificphotodamage AT waleskakerllenmartins enhancedefficiencyofcelldeathbylysosomespecificphotodamage AT christianepavani enhancedefficiencyofcelldeathbylysosomespecificphotodamage AT helenacoutojunqueira enhancedefficiencyofcelldeathbylysosomespecificphotodamage AT rosangelaitri enhancedefficiencyofcelldeathbylysosomespecificphotodamage AT mauriciosbaptista enhancedefficiencyofcelldeathbylysosomespecificphotodamage
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Enhanced efficiency of cell death by lysosome-specific photodamage

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