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Differentiation-dependent photodynamic therapy regulated by porphobilinogen deaminase in B16 melanoma

Protoporphyrin IX (PpIX) synthesis by malignant cells is clinically exploited for photodiagnosis and photodynamic therapy following administration of 5-aminolevulinic acid (ALA). The expression and activity of the housekeeping porphobilinogen deaminase (PBGD) was correlated to PpIX synthesis in diff...

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Autores principales: Ickowicz Schwartz, D, Gozlan, Y, Greenbaum, L, Babushkina, T, Katcoff, D J, Malik, Z
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409749/
https://www.ncbi.nlm.nih.gov/pubmed/15150593
http://dx.doi.org/10.1038/sj.bjc.6601760
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author Ickowicz Schwartz, D
Gozlan, Y
Greenbaum, L
Babushkina, T
Katcoff, D J
Malik, Z
author_facet Ickowicz Schwartz, D
Gozlan, Y
Greenbaum, L
Babushkina, T
Katcoff, D J
Malik, Z
author_sort Ickowicz Schwartz, D
collection PubMed
description Protoporphyrin IX (PpIX) synthesis by malignant cells is clinically exploited for photodiagnosis and photodynamic therapy following administration of 5-aminolevulinic acid (ALA). The expression and activity of the housekeeping porphobilinogen deaminase (PBGD) was correlated to PpIX synthesis in differentiating B16 melanoma cells. Differentiation was stimulated by two inducers, butyrate and hexamethylene bisacetamide (HMBA), both of which promote the formation of typical melanosomes and melanin, as well as morphological changeover. A marked decrease in total PBGD activity and PpIX synthesis was observed following stimulation by butyrate, while HMBA induced an opposite effect. In contrast, ferrochelatase levels remained unchanged. Photodynamic inactivation of the cells undergoing differentiation was largely dependent on the PpIX accumulation, which was modulated by the two inducers butyrate and HMBA. Fluorescence immunostaining with anti-PBGD antibodies revealed a major PBGD fraction in the nucleus and a minor fraction in the cytosol. This nuclear localisation pattern was confirmed by expression of PBGD fused to green fluorescence protein. We suggest that efficient photodynamic therapy of cancer facilitated by ALA administration can be enhanced using combined therapeutic modalities.
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spelling pubmed-24097492009-09-10 Differentiation-dependent photodynamic therapy regulated by porphobilinogen deaminase in B16 melanoma Ickowicz Schwartz, D Gozlan, Y Greenbaum, L Babushkina, T Katcoff, D J Malik, Z Br J Cancer Experimental Therapeutics Protoporphyrin IX (PpIX) synthesis by malignant cells is clinically exploited for photodiagnosis and photodynamic therapy following administration of 5-aminolevulinic acid (ALA). The expression and activity of the housekeeping porphobilinogen deaminase (PBGD) was correlated to PpIX synthesis in differentiating B16 melanoma cells. Differentiation was stimulated by two inducers, butyrate and hexamethylene bisacetamide (HMBA), both of which promote the formation of typical melanosomes and melanin, as well as morphological changeover. A marked decrease in total PBGD activity and PpIX synthesis was observed following stimulation by butyrate, while HMBA induced an opposite effect. In contrast, ferrochelatase levels remained unchanged. Photodynamic inactivation of the cells undergoing differentiation was largely dependent on the PpIX accumulation, which was modulated by the two inducers butyrate and HMBA. Fluorescence immunostaining with anti-PBGD antibodies revealed a major PBGD fraction in the nucleus and a minor fraction in the cytosol. This nuclear localisation pattern was confirmed by expression of PBGD fused to green fluorescence protein. We suggest that efficient photodynamic therapy of cancer facilitated by ALA administration can be enhanced using combined therapeutic modalities. Nature Publishing Group 2004-05-04 2004-04-06 /pmc/articles/PMC2409749/ /pubmed/15150593 http://dx.doi.org/10.1038/sj.bjc.6601760 Text en Copyright © 2004 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Experimental Therapeutics
Ickowicz Schwartz, D
Gozlan, Y
Greenbaum, L
Babushkina, T
Katcoff, D J
Malik, Z
Differentiation-dependent photodynamic therapy regulated by porphobilinogen deaminase in B16 melanoma
title Differentiation-dependent photodynamic therapy regulated by porphobilinogen deaminase in B16 melanoma
title_full Differentiation-dependent photodynamic therapy regulated by porphobilinogen deaminase in B16 melanoma
title_fullStr Differentiation-dependent photodynamic therapy regulated by porphobilinogen deaminase in B16 melanoma
title_full_unstemmed Differentiation-dependent photodynamic therapy regulated by porphobilinogen deaminase in B16 melanoma
title_short Differentiation-dependent photodynamic therapy regulated by porphobilinogen deaminase in B16 melanoma
title_sort differentiation-dependent photodynamic therapy regulated by porphobilinogen deaminase in b16 melanoma
topic Experimental Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409749/
https://www.ncbi.nlm.nih.gov/pubmed/15150593
http://dx.doi.org/10.1038/sj.bjc.6601760
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