Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-β-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells

Autores
Weiz, Gisela; Gonzalez, Alina Lujan; Mansilla, Iara Soledad; Fernandez Zapico, Martin Ernesto; Molejon, Maria Ines; Breccia, Javier Dario
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background Low targeting efcacy and high toxicity continue to be challenges in Oncology. A promising strat‑ egy is the glycosylation of chemotherapeutic agents to improve their pharmacodynamics and anti-tumoral activity. Herein, we provide evidence of a novel approach using diglycosidases from fungi of the Hypocreales order to obtain novel rutinose-conjugates therapeutic agents with enhanced anti-tumoral capacity. Results Screening for diglycosidase activity in twenty-eight strains of the genetically related genera Acremonium and Sarocladium identifed 6-O-α-rhamnosyl-β-glucosidase (αRβG) of Sarocladium strictum DMic 093557 as candidate enzyme for our studies. Biochemically characterization shows that αRβG has the ability to transglycosylate bulky OH-acceptors, including bioactive compounds. Interestingly, rutinoside-derivatives of phloroglucinol (PR) resor‑ cinol (RR) and 4-methylumbelliferone (4MUR) displayed higher growth inhibitory activity on pancreatic cancer cells than the respective aglycones without signifcant afecting normal pancreatic epithelial cells. PR exhibited the highest efcacy with an IC50 of 0.89 mM, followed by RR with an IC50 of 1.67 mM, and 4MUR with an IC50 of 2.4 mM, whereas the respective aglycones displayed higher IC50 values: 4.69 mM for phloroglucinol, 5.90 mM for resorcinol, and 4.8 mM for 4-methylumbelliferone. Further, glycoconjugates signifcantly sensitized pancreatic cancer cells to the standard of care chemotherapy agent gemcitabine. Conclusions αRβG from S. strictum transglycosylate-based approach to synthesize rutinosides represents a suit‑ able option to enhance the anti-proliferative efect of bioactive compounds. This fnding opens up new possibilities for developing more efective therapies for pancreatic cancer and other solid malignancies.
Fil: Weiz, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina
Fil: Gonzalez, Alina Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina
Fil: Mansilla, Iara Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina
Fil: Fernandez Zapico, Martin Ernesto. Mayo Clinic Cancer Center; Estados Unidos
Fil: Molejon, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina
Fil: Breccia, Javier Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina
Materia
RUTINOSIDES
TRANSGLYCOSYLATION
TUMORAL CELLS
DIGLYCOSIDASES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/264612
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-β-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cellsWeiz, GiselaGonzalez, Alina LujanMansilla, Iara SoledadFernandez Zapico, Martin ErnestoMolejon, Maria InesBreccia, Javier DarioRUTINOSIDESTRANSGLYCOSYLATIONTUMORAL CELLSDIGLYCOSIDASEShttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Background Low targeting efcacy and high toxicity continue to be challenges in Oncology. A promising strat‑ egy is the glycosylation of chemotherapeutic agents to improve their pharmacodynamics and anti-tumoral activity. Herein, we provide evidence of a novel approach using diglycosidases from fungi of the Hypocreales order to obtain novel rutinose-conjugates therapeutic agents with enhanced anti-tumoral capacity. Results Screening for diglycosidase activity in twenty-eight strains of the genetically related genera Acremonium and Sarocladium identifed 6-O-α-rhamnosyl-β-glucosidase (αRβG) of Sarocladium strictum DMic 093557 as candidate enzyme for our studies. Biochemically characterization shows that αRβG has the ability to transglycosylate bulky OH-acceptors, including bioactive compounds. Interestingly, rutinoside-derivatives of phloroglucinol (PR) resor‑ cinol (RR) and 4-methylumbelliferone (4MUR) displayed higher growth inhibitory activity on pancreatic cancer cells than the respective aglycones without signifcant afecting normal pancreatic epithelial cells. PR exhibited the highest efcacy with an IC50 of 0.89 mM, followed by RR with an IC50 of 1.67 mM, and 4MUR with an IC50 of 2.4 mM, whereas the respective aglycones displayed higher IC50 values: 4.69 mM for phloroglucinol, 5.90 mM for resorcinol, and 4.8 mM for 4-methylumbelliferone. Further, glycoconjugates signifcantly sensitized pancreatic cancer cells to the standard of care chemotherapy agent gemcitabine. Conclusions αRβG from S. strictum transglycosylate-based approach to synthesize rutinosides represents a suit‑ able option to enhance the anti-proliferative efect of bioactive compounds. This fnding opens up new possibilities for developing more efective therapies for pancreatic cancer and other solid malignancies.Fil: Weiz, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; ArgentinaFil: Gonzalez, Alina Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; ArgentinaFil: Mansilla, Iara Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; ArgentinaFil: Fernandez Zapico, Martin Ernesto. Mayo Clinic Cancer Center; Estados UnidosFil: Molejon, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; ArgentinaFil: Breccia, Javier Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; ArgentinaBioMed Central2024-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/264612Weiz, Gisela; Gonzalez, Alina Lujan; Mansilla, Iara Soledad; Fernandez Zapico, Martin Ernesto; Molejon, Maria Ines; et al.; Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-β-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells; BioMed Central; Microbial Cell Factories; 23; 1; 5-2024; 133-1451475-2859CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-024-02395-0info:eu-repo/semantics/altIdentifier/doi/10.1186/s12934-024-02395-0info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:22:59Zoai:ri.conicet.gov.ar:11336/264612instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:23:00.272CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-β-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells
title Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-β-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells
spellingShingle Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-β-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells
Weiz, Gisela
RUTINOSIDES
TRANSGLYCOSYLATION
TUMORAL CELLS
DIGLYCOSIDASES
title_short Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-β-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells
title_full Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-β-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells
title_fullStr Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-β-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells
title_full_unstemmed Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-β-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells
title_sort Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-β-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells
dc.creator.none.fl_str_mv Weiz, Gisela
Gonzalez, Alina Lujan
Mansilla, Iara Soledad
Fernandez Zapico, Martin Ernesto
Molejon, Maria Ines
Breccia, Javier Dario
author Weiz, Gisela
author_facet Weiz, Gisela
Gonzalez, Alina Lujan
Mansilla, Iara Soledad
Fernandez Zapico, Martin Ernesto
Molejon, Maria Ines
Breccia, Javier Dario
author_role author
author2 Gonzalez, Alina Lujan
Mansilla, Iara Soledad
Fernandez Zapico, Martin Ernesto
Molejon, Maria Ines
Breccia, Javier Dario
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv RUTINOSIDES
TRANSGLYCOSYLATION
TUMORAL CELLS
DIGLYCOSIDASES
topic RUTINOSIDES
TRANSGLYCOSYLATION
TUMORAL CELLS
DIGLYCOSIDASES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background Low targeting efcacy and high toxicity continue to be challenges in Oncology. A promising strat‑ egy is the glycosylation of chemotherapeutic agents to improve their pharmacodynamics and anti-tumoral activity. Herein, we provide evidence of a novel approach using diglycosidases from fungi of the Hypocreales order to obtain novel rutinose-conjugates therapeutic agents with enhanced anti-tumoral capacity. Results Screening for diglycosidase activity in twenty-eight strains of the genetically related genera Acremonium and Sarocladium identifed 6-O-α-rhamnosyl-β-glucosidase (αRβG) of Sarocladium strictum DMic 093557 as candidate enzyme for our studies. Biochemically characterization shows that αRβG has the ability to transglycosylate bulky OH-acceptors, including bioactive compounds. Interestingly, rutinoside-derivatives of phloroglucinol (PR) resor‑ cinol (RR) and 4-methylumbelliferone (4MUR) displayed higher growth inhibitory activity on pancreatic cancer cells than the respective aglycones without signifcant afecting normal pancreatic epithelial cells. PR exhibited the highest efcacy with an IC50 of 0.89 mM, followed by RR with an IC50 of 1.67 mM, and 4MUR with an IC50 of 2.4 mM, whereas the respective aglycones displayed higher IC50 values: 4.69 mM for phloroglucinol, 5.90 mM for resorcinol, and 4.8 mM for 4-methylumbelliferone. Further, glycoconjugates signifcantly sensitized pancreatic cancer cells to the standard of care chemotherapy agent gemcitabine. Conclusions αRβG from S. strictum transglycosylate-based approach to synthesize rutinosides represents a suit‑ able option to enhance the anti-proliferative efect of bioactive compounds. This fnding opens up new possibilities for developing more efective therapies for pancreatic cancer and other solid malignancies.
Fil: Weiz, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina
Fil: Gonzalez, Alina Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina
Fil: Mansilla, Iara Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina
Fil: Fernandez Zapico, Martin Ernesto. Mayo Clinic Cancer Center; Estados Unidos
Fil: Molejon, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina
Fil: Breccia, Javier Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina
description Background Low targeting efcacy and high toxicity continue to be challenges in Oncology. A promising strat‑ egy is the glycosylation of chemotherapeutic agents to improve their pharmacodynamics and anti-tumoral activity. Herein, we provide evidence of a novel approach using diglycosidases from fungi of the Hypocreales order to obtain novel rutinose-conjugates therapeutic agents with enhanced anti-tumoral capacity. Results Screening for diglycosidase activity in twenty-eight strains of the genetically related genera Acremonium and Sarocladium identifed 6-O-α-rhamnosyl-β-glucosidase (αRβG) of Sarocladium strictum DMic 093557 as candidate enzyme for our studies. Biochemically characterization shows that αRβG has the ability to transglycosylate bulky OH-acceptors, including bioactive compounds. Interestingly, rutinoside-derivatives of phloroglucinol (PR) resor‑ cinol (RR) and 4-methylumbelliferone (4MUR) displayed higher growth inhibitory activity on pancreatic cancer cells than the respective aglycones without signifcant afecting normal pancreatic epithelial cells. PR exhibited the highest efcacy with an IC50 of 0.89 mM, followed by RR with an IC50 of 1.67 mM, and 4MUR with an IC50 of 2.4 mM, whereas the respective aglycones displayed higher IC50 values: 4.69 mM for phloroglucinol, 5.90 mM for resorcinol, and 4.8 mM for 4-methylumbelliferone. Further, glycoconjugates signifcantly sensitized pancreatic cancer cells to the standard of care chemotherapy agent gemcitabine. Conclusions αRβG from S. strictum transglycosylate-based approach to synthesize rutinosides represents a suit‑ able option to enhance the anti-proliferative efect of bioactive compounds. This fnding opens up new possibilities for developing more efective therapies for pancreatic cancer and other solid malignancies.
publishDate 2024
dc.date.none.fl_str_mv 2024-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/264612
Weiz, Gisela; Gonzalez, Alina Lujan; Mansilla, Iara Soledad; Fernandez Zapico, Martin Ernesto; Molejon, Maria Ines; et al.; Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-β-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells; BioMed Central; Microbial Cell Factories; 23; 1; 5-2024; 133-145
1475-2859
CONICET Digital
CONICET
url http://hdl.handle.net/11336/264612
identifier_str_mv Weiz, Gisela; Gonzalez, Alina Lujan; Mansilla, Iara Soledad; Fernandez Zapico, Martin Ernesto; Molejon, Maria Ines; et al.; Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-β-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells; BioMed Central; Microbial Cell Factories; 23; 1; 5-2024; 133-145
1475-2859
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1186/s12934-024-02395-0
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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