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Natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of Patched and increase chemotherapy efficiency on melanoma cells

Multidrug resistance has appeared to mitigate the efficiency of anticancer drugs and the possibility of successful cancer chemotherapy. The Hedgehog receptor Patched is a multidrug transporter expressed in several cancers and as such it represents a new target to circumvent chemotherapy resistance....

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Autores principales: Fiorini, Laura, Tribalat, Marie-Aude, Sauvard, Lucy, Cazareth, Julie, Lalli, Enzo, Broutin, Isabelle, Thomas, Olivier P., Mus-Veteau, Isabelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673163/
https://www.ncbi.nlm.nih.gov/pubmed/26068979
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author Fiorini, Laura
Tribalat, Marie-Aude
Sauvard, Lucy
Cazareth, Julie
Lalli, Enzo
Broutin, Isabelle
Thomas, Olivier P.
Mus-Veteau, Isabelle
author_facet Fiorini, Laura
Tribalat, Marie-Aude
Sauvard, Lucy
Cazareth, Julie
Lalli, Enzo
Broutin, Isabelle
Thomas, Olivier P.
Mus-Veteau, Isabelle
author_sort Fiorini, Laura
collection PubMed
description Multidrug resistance has appeared to mitigate the efficiency of anticancer drugs and the possibility of successful cancer chemotherapy. The Hedgehog receptor Patched is a multidrug transporter expressed in several cancers and as such it represents a new target to circumvent chemotherapy resistance. We report herein that paniceins and especially panicein A hydroquinone, natural meroterpenoids produced by the Mediterranean sponge Haliclona (Soestella) mucosa, inhibit the doxorubicin efflux activity of Patched and enhance the cytotoxicity of this chemotherapeutic agent on melanoma cells in vitro. These results are supported by the molecular docking performed on the structure of the bacterial drug efflux pump AcrB and on the Patched model built from AcrB structure. Docking calculations show that panicein A hydroquinone interacts with AcrB and Patched model close to the doxorubicin binding site. This compound thus appears as the first antagonist of the doxorubicin efflux activity of Patched. The use of inhibitors of Patched drug efflux activity in combination with classical chemotherapy could represent a novel approach to reduce tumor drug resistance, recurrence and metastasis.
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spelling pubmed-46731632015-12-23 Natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of Patched and increase chemotherapy efficiency on melanoma cells Fiorini, Laura Tribalat, Marie-Aude Sauvard, Lucy Cazareth, Julie Lalli, Enzo Broutin, Isabelle Thomas, Olivier P. Mus-Veteau, Isabelle Oncotarget Research Paper Multidrug resistance has appeared to mitigate the efficiency of anticancer drugs and the possibility of successful cancer chemotherapy. The Hedgehog receptor Patched is a multidrug transporter expressed in several cancers and as such it represents a new target to circumvent chemotherapy resistance. We report herein that paniceins and especially panicein A hydroquinone, natural meroterpenoids produced by the Mediterranean sponge Haliclona (Soestella) mucosa, inhibit the doxorubicin efflux activity of Patched and enhance the cytotoxicity of this chemotherapeutic agent on melanoma cells in vitro. These results are supported by the molecular docking performed on the structure of the bacterial drug efflux pump AcrB and on the Patched model built from AcrB structure. Docking calculations show that panicein A hydroquinone interacts with AcrB and Patched model close to the doxorubicin binding site. This compound thus appears as the first antagonist of the doxorubicin efflux activity of Patched. The use of inhibitors of Patched drug efflux activity in combination with classical chemotherapy could represent a novel approach to reduce tumor drug resistance, recurrence and metastasis. Impact Journals LLC 2015-06-01 /pmc/articles/PMC4673163/ /pubmed/26068979 Text en Copyright: © 2015 Fiorini et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Fiorini, Laura
Tribalat, Marie-Aude
Sauvard, Lucy
Cazareth, Julie
Lalli, Enzo
Broutin, Isabelle
Thomas, Olivier P.
Mus-Veteau, Isabelle
Natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of Patched and increase chemotherapy efficiency on melanoma cells
title Natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of Patched and increase chemotherapy efficiency on melanoma cells
title_full Natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of Patched and increase chemotherapy efficiency on melanoma cells
title_fullStr Natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of Patched and increase chemotherapy efficiency on melanoma cells
title_full_unstemmed Natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of Patched and increase chemotherapy efficiency on melanoma cells
title_short Natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of Patched and increase chemotherapy efficiency on melanoma cells
title_sort natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of patched and increase chemotherapy efficiency on melanoma cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673163/
https://www.ncbi.nlm.nih.gov/pubmed/26068979
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