Targeting the Tumor Extracellular Matrix by the Natural Molecule 4-Methylumbelliferone: A Complementary and Alternative Cancer Therapeutic Strategy

In antineoplastic therapy, one of the challenges is to adjust the treatment to the needs of each patient and reduce the toxicity caused by conventional antitumor strategies. It has been demonstrated that natural products with antitumoral properties are less toxic than chemotherapy and radiotherap...

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Autores principales: Vitale, Daiana Luján, Icardi, Antonella, Rosales, Paolo, Spinelli, Fiorella Mercedes, Sevic, Ina, Alaniz, Laura
Otros Autores: 0000-0001-5593-9101
Formato: Artículo publishedVersion
Lenguaje:Inglés
Publicado: 2023
Materias:
4-methylumbelliferone
Hyaluronan
Extracellular matrix
Cancer
Antitumoral action
Acceso en línea:http://repositorio.unnoba.edu.ar/xmlui/handle/23601/633
Aporte de:
Re DI Repositorio Digital UNNOBA de Universidad Nacional del Noroeste de la Provincia de Buenos Aires
id I103-R405-23601-633
record_format dspace
institution Universidad Nacional del Noroeste de la Provincia de Buenos Aires
institution_str I-103
repository_str R-405
collection Re DI Repositorio Digital UNNOBA
language Inglés
topic 4-methylumbelliferone
Hyaluronan
Extracellular matrix
Cancer
Antitumoral action
spellingShingle 4-methylumbelliferone
Hyaluronan
Extracellular matrix
Cancer
Antitumoral action
Vitale, Daiana Luján
Icardi, Antonella
Rosales, Paolo
Spinelli, Fiorella Mercedes
Sevic, Ina
Alaniz, Laura
Targeting the Tumor Extracellular Matrix by the Natural Molecule 4-Methylumbelliferone: A Complementary and Alternative Cancer Therapeutic Strategy
topic_facet 4-methylumbelliferone
Hyaluronan
Extracellular matrix
Cancer
Antitumoral action
description In antineoplastic therapy, one of the challenges is to adjust the treatment to the needs of each patient and reduce the toxicity caused by conventional antitumor strategies. It has been demonstrated that natural products with antitumoral properties are less toxic than chemotherapy and radiotherapy. Also, using already developed drugs allows developing substantially less costly methods for the discovery of new treatments than traditional drug development. Candidate molecules proposed for drug repositioning include 4- methylumbelliferone (4-MU), an orally available dietetic product, derivative of coumarin and mainly found in the plant family Umbelliferae or Apiaceae. 4-MU specifically inhibits the synthesis of glycosaminoglycan hyaluronan (HA), which is its main mechanism of action. This agent reduces the availability of HA substrates and inhibits the activity of different HA synthases. However, an effect independent of HA synthesis has also been observed. 4- MU acts as an inhibitor of tumor growth in different types of cancer. Particularly, 4-MU acts on the proliferation, migration and invasion abilities of tumor cells and inhibits the progression of cancer stem cells and the development of drug resistance. In addition, the effect of 4-MU impacts not only on tumor cells, but also on other components of the tumor microenvironment. Specifically, 4-MU can potentially act on immune, fibroblast and endothelial cells, and pro-tumor processes such as angiogenesis. Most of these effects are consistent with the altered functions of HA during tumor progression and can be interrupted by the action of 4-MU. While the potential advantage of 4-MU as an adjunct in cancer therapy could improve therapeutic efficacy and reduce toxicities of other antitumoral agents, the greatest challenge is the lack of scientific evidence to support its approval. Therefore, crucial human clinical studies have yet to be done to respond to this need. Here, we discuss and review the possible applications of 4-MU as an adjunct in conventional antineoplastic therapies, to achieve greater therapeutic success. We also describe the main proposed mechanisms of action that promote an increase in the efficacy of conventional antineoplastic strategies in different types of cancer and prospects that promote 4-MU repositioning and application in cancer therapy.
author2 0000-0001-5593-9101
author_facet 0000-0001-5593-9101
Vitale, Daiana Luján
Icardi, Antonella
Rosales, Paolo
Spinelli, Fiorella Mercedes
Sevic, Ina
Alaniz, Laura
format Artículo
Artículo
publishedVersion
Artículo
Artículo
publishedVersion
Artículo
Artículo
publishedVersion
author Vitale, Daiana Luján
Icardi, Antonella
Rosales, Paolo
Spinelli, Fiorella Mercedes
Sevic, Ina
Alaniz, Laura
author_sort Vitale, Daiana Luján
title Targeting the Tumor Extracellular Matrix by the Natural Molecule 4-Methylumbelliferone: A Complementary and Alternative Cancer Therapeutic Strategy
title_short Targeting the Tumor Extracellular Matrix by the Natural Molecule 4-Methylumbelliferone: A Complementary and Alternative Cancer Therapeutic Strategy
title_full Targeting the Tumor Extracellular Matrix by the Natural Molecule 4-Methylumbelliferone: A Complementary and Alternative Cancer Therapeutic Strategy
title_fullStr Targeting the Tumor Extracellular Matrix by the Natural Molecule 4-Methylumbelliferone: A Complementary and Alternative Cancer Therapeutic Strategy
title_full_unstemmed Targeting the Tumor Extracellular Matrix by the Natural Molecule 4-Methylumbelliferone: A Complementary and Alternative Cancer Therapeutic Strategy
title_sort targeting the tumor extracellular matrix by the natural molecule 4-methylumbelliferone: a complementary and alternative cancer therapeutic strategy
publishDate 2023
url http://repositorio.unnoba.edu.ar/xmlui/handle/23601/633
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spelling I103-R405-23601-6332025-10-21T21:10:35Z Targeting the Tumor Extracellular Matrix by the Natural Molecule 4-Methylumbelliferone: A Complementary and Alternative Cancer Therapeutic Strategy Vitale, Daiana Luján Icardi, Antonella Rosales, Paolo Spinelli, Fiorella Mercedes Sevic, Ina Alaniz, Laura 0000-0001-5593-9101 0000-0002-6070-6078 4-methylumbelliferone Hyaluronan Extracellular matrix Cancer Antitumoral action In antineoplastic therapy, one of the challenges is to adjust the treatment to the needs of each patient and reduce the toxicity caused by conventional antitumor strategies. It has been demonstrated that natural products with antitumoral properties are less toxic than chemotherapy and radiotherapy. Also, using already developed drugs allows developing substantially less costly methods for the discovery of new treatments than traditional drug development. Candidate molecules proposed for drug repositioning include 4- methylumbelliferone (4-MU), an orally available dietetic product, derivative of coumarin and mainly found in the plant family Umbelliferae or Apiaceae. 4-MU specifically inhibits the synthesis of glycosaminoglycan hyaluronan (HA), which is its main mechanism of action. This agent reduces the availability of HA substrates and inhibits the activity of different HA synthases. However, an effect independent of HA synthesis has also been observed. 4- MU acts as an inhibitor of tumor growth in different types of cancer. Particularly, 4-MU acts on the proliferation, migration and invasion abilities of tumor cells and inhibits the progression of cancer stem cells and the development of drug resistance. In addition, the effect of 4-MU impacts not only on tumor cells, but also on other components of the tumor microenvironment. Specifically, 4-MU can potentially act on immune, fibroblast and endothelial cells, and pro-tumor processes such as angiogenesis. Most of these effects are consistent with the altered functions of HA during tumor progression and can be interrupted by the action of 4-MU. While the potential advantage of 4-MU as an adjunct in cancer therapy could improve therapeutic efficacy and reduce toxicities of other antitumoral agents, the greatest challenge is the lack of scientific evidence to support its approval. Therefore, crucial human clinical studies have yet to be done to respond to this need. Here, we discuss and review the possible applications of 4-MU as an adjunct in conventional antineoplastic therapies, to achieve greater therapeutic success. We also describe the main proposed mechanisms of action that promote an increase in the efficacy of conventional antineoplastic strategies in different types of cancer and prospects that promote 4-MU repositioning and application in cancer therapy. Fil: Vitale, Daiana Luján. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Vitale, Daiana Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Icardi, Antonella. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Icardi, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Rosales, Paolo. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Rosales, Paolo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Spinelli, Fiorella Mercedes. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Spinelli, Fiorella Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Sevic, Ina. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Sevic, Ina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Alaniz, Laura. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Alaniz, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Con referato 2023-12-04T19:03:56Z 2023-12-04T19:03:56Z 2021-10-04 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion Vitale D. L., Icardi A., Rosales P., Spinelli F. M., Sevic I., Alaniz L. D. (2021). Targeting the Tumor Extracellular Matrix by the Natural Molecule 4-Methylumbelliferone: A Complementary and Alternative Cancer Therapeutic Strategy. Frontiers in Oncology, 11(710061) 2234-943X http://repositorio.unnoba.edu.ar/xmlui/handle/23601/633 eng eu-repo/grantAgreement/UNNOBA/SIB 2019/0561-2019 eu-repo/grantAgreement/ ANPCyT/PICTO/2019-00011 doi: 10.3389/fonc.2021.710061 info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ application/pdf application/pdf Frontiers in Oncology

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