Macrocyclic lactones inhibit nasopharyngeal carcinoma cells proliferation through PAK1 inhibition and reduce in vivo tumor growth
International audience Purpose: The Epstein-Barr virus (EBV)-associated cancer nasopharyngeal carcinoma (NPC) is rare in Europe and North America but is a real public health problem in some regions of the world, such as southern Asia, North Africa, and for Inuit populations. Due to the anatomy and l...
Published in: | Drug Design, Development and Therapy |
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Online Access: | https://hal.inrae.fr/hal-02621025 https://hal.inrae.fr/hal-02621025/document https://hal.inrae.fr/hal-02621025/file/Gallardo-DDDT-2018_1.pdf https://doi.org/10.2147/DDDT.S172538 |
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ftunivnantes:oai:HAL:hal-02621025v1 2023-05-15T16:55:14+02:00 Macrocyclic lactones inhibit nasopharyngeal carcinoma cells proliferation through PAK1 inhibition and reduce in vivo tumor growth Gallardo, Franck Mariamé, Bernard Gence, Rémi Tilkin-Mariamé, Anne-Francoise NeoVirTech (FRANCE) Laboratoire de biologie moléculaire eucaryote (LBME) Université Toulouse III - Paul Sabatier (UT3) Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI) Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) Institut des Technologies Avancées en sciences du Vivant (ITAV) Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS) Centre de Recherches en Cancérologie de Toulouse (CRCT) Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) Institut National de la Santé et de la Recherche Médicale (INSERM) 2018 https://hal.inrae.fr/hal-02621025 https://hal.inrae.fr/hal-02621025/document https://hal.inrae.fr/hal-02621025/file/Gallardo-DDDT-2018_1.pdf https://doi.org/10.2147/DDDT.S172538 en eng HAL CCSD Dove Medical Press info:eu-repo/semantics/altIdentifier/doi/10.2147/DDDT.S172538 hal-02621025 https://hal.inrae.fr/hal-02621025 https://hal.inrae.fr/hal-02621025/document https://hal.inrae.fr/hal-02621025/file/Gallardo-DDDT-2018_1.pdf doi:10.2147/DDDT.S172538 PRODINRA: 453328 WOS: 000444034300001 http://creativecommons.org/licenses/by-nc/ info:eu-repo/semantics/OpenAccess CC-BY-NC ISSN: 1177-8881 Drug Design, Development and Therapy https://hal.inrae.fr/hal-02621025 Drug Design, Development and Therapy, 2018, 12, pp.2805-2814. ⟨10.2147/DDDT.S172538⟩ [SDV]Life Sciences [q-bio] info:eu-repo/semantics/article Journal articles 2018 ftunivnantes https://doi.org/10.2147/DDDT.S172538 2023-02-22T06:46:57Z International audience Purpose: The Epstein-Barr virus (EBV)-associated cancer nasopharyngeal carcinoma (NPC) is rare in Europe and North America but is a real public health problem in some regions of the world, such as southern Asia, North Africa, and for Inuit populations. Due to the anatomy and location of the nasopharynx, surgery is rarely used to treat primary NPC cancers. Treatment by radiotherapy, combined or not with chemotherapy, are efficient for primary tumors but often do not protect against fatal relapses or metastases. Methods: Search for new therapeutic molecules through high content screening lead to the identification of Ivermectin (IVM) as a promising drug. IVM is a US Food and Drug Administration-approved macrocyclic lactone widely used as anthelmintic and insecticidal agent that has also shown protective effects against cancers. Results: We show here that IVM has cytotoxic activity in vitro against NPC cells, in which it reduces MAPKs pathway activation through the inhibition PAK-1 activity. Moreover, all macrocyclic lactones tested and a PAK1 inhibitor are cytotoxic in vitro for EBV-positive and EBV-negative NPC tumor cells. We have also shown that IVM intraperitoneal repeated injections, at US Food and Drug Administration-approved doses, have no significant toxicity and decrease NPC subcutaneous tumors development in nude mice. Conclusion: Macrocyclic lactones appear as promising molecules against NPC targeting PAK-1 with no detectable adverse effect. Article in Journal/Newspaper inuit Université de Nantes: HAL-UNIV-NANTES Drug Design, Development and Therapy Volume 12 2805 2814 |
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Université de Nantes: HAL-UNIV-NANTES |
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English |
topic |
[SDV]Life Sciences [q-bio] |
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[SDV]Life Sciences [q-bio] Gallardo, Franck Mariamé, Bernard Gence, Rémi Tilkin-Mariamé, Anne-Francoise Macrocyclic lactones inhibit nasopharyngeal carcinoma cells proliferation through PAK1 inhibition and reduce in vivo tumor growth |
topic_facet |
[SDV]Life Sciences [q-bio] |
description |
International audience Purpose: The Epstein-Barr virus (EBV)-associated cancer nasopharyngeal carcinoma (NPC) is rare in Europe and North America but is a real public health problem in some regions of the world, such as southern Asia, North Africa, and for Inuit populations. Due to the anatomy and location of the nasopharynx, surgery is rarely used to treat primary NPC cancers. Treatment by radiotherapy, combined or not with chemotherapy, are efficient for primary tumors but often do not protect against fatal relapses or metastases. Methods: Search for new therapeutic molecules through high content screening lead to the identification of Ivermectin (IVM) as a promising drug. IVM is a US Food and Drug Administration-approved macrocyclic lactone widely used as anthelmintic and insecticidal agent that has also shown protective effects against cancers. Results: We show here that IVM has cytotoxic activity in vitro against NPC cells, in which it reduces MAPKs pathway activation through the inhibition PAK-1 activity. Moreover, all macrocyclic lactones tested and a PAK1 inhibitor are cytotoxic in vitro for EBV-positive and EBV-negative NPC tumor cells. We have also shown that IVM intraperitoneal repeated injections, at US Food and Drug Administration-approved doses, have no significant toxicity and decrease NPC subcutaneous tumors development in nude mice. Conclusion: Macrocyclic lactones appear as promising molecules against NPC targeting PAK-1 with no detectable adverse effect. |
author2 |
NeoVirTech (FRANCE) Laboratoire de biologie moléculaire eucaryote (LBME) Université Toulouse III - Paul Sabatier (UT3) Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI) Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) Institut des Technologies Avancées en sciences du Vivant (ITAV) Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS) Centre de Recherches en Cancérologie de Toulouse (CRCT) Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) Institut National de la Santé et de la Recherche Médicale (INSERM) |
format |
Article in Journal/Newspaper |
author |
Gallardo, Franck Mariamé, Bernard Gence, Rémi Tilkin-Mariamé, Anne-Francoise |
author_facet |
Gallardo, Franck Mariamé, Bernard Gence, Rémi Tilkin-Mariamé, Anne-Francoise |
author_sort |
Gallardo, Franck |
title |
Macrocyclic lactones inhibit nasopharyngeal carcinoma cells proliferation through PAK1 inhibition and reduce in vivo tumor growth |
title_short |
Macrocyclic lactones inhibit nasopharyngeal carcinoma cells proliferation through PAK1 inhibition and reduce in vivo tumor growth |
title_full |
Macrocyclic lactones inhibit nasopharyngeal carcinoma cells proliferation through PAK1 inhibition and reduce in vivo tumor growth |
title_fullStr |
Macrocyclic lactones inhibit nasopharyngeal carcinoma cells proliferation through PAK1 inhibition and reduce in vivo tumor growth |
title_full_unstemmed |
Macrocyclic lactones inhibit nasopharyngeal carcinoma cells proliferation through PAK1 inhibition and reduce in vivo tumor growth |
title_sort |
macrocyclic lactones inhibit nasopharyngeal carcinoma cells proliferation through pak1 inhibition and reduce in vivo tumor growth |
publisher |
HAL CCSD |
publishDate |
2018 |
url |
https://hal.inrae.fr/hal-02621025 https://hal.inrae.fr/hal-02621025/document https://hal.inrae.fr/hal-02621025/file/Gallardo-DDDT-2018_1.pdf https://doi.org/10.2147/DDDT.S172538 |
genre |
inuit |
genre_facet |
inuit |
op_source |
ISSN: 1177-8881 Drug Design, Development and Therapy https://hal.inrae.fr/hal-02621025 Drug Design, Development and Therapy, 2018, 12, pp.2805-2814. ⟨10.2147/DDDT.S172538⟩ |
op_relation |
info:eu-repo/semantics/altIdentifier/doi/10.2147/DDDT.S172538 hal-02621025 https://hal.inrae.fr/hal-02621025 https://hal.inrae.fr/hal-02621025/document https://hal.inrae.fr/hal-02621025/file/Gallardo-DDDT-2018_1.pdf doi:10.2147/DDDT.S172538 PRODINRA: 453328 WOS: 000444034300001 |
op_rights |
http://creativecommons.org/licenses/by-nc/ info:eu-repo/semantics/OpenAccess |
op_rightsnorm |
CC-BY-NC |
op_doi |
https://doi.org/10.2147/DDDT.S172538 |
container_title |
Drug Design, Development and Therapy |
container_volume |
Volume 12 |
container_start_page |
2805 |
op_container_end_page |
2814 |
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1766046216222670848 |