Cargando…

Synergistic Antitumorigenic Activity of Calcitriol with Curcumin or Resveratrol is Mediated by Angiogenesis Inhibition in Triple Negative Breast Cancer Xenografts

Calcitriol is a multitarget anticancer hormone; however, its effects on angiogenesis remain contradictory. Herein, we tested whether the antiangiogenic phytochemicals curcumin or resveratrol improved calcitriol antitumorigenic effects in vivo. Triple-negative breast cancer tumoral cells (MBCDF-T) we...

Descripción completa

Detalles Bibliográficos
Autores principales: García-Quiroz, Janice, García-Becerra, Rocío, Santos-Cuevas, Clara, Ramírez-Nava, Gerardo J., Morales-Guadarrama, Gabriela, Cárdenas-Ochoa, Nohemí, Segovia-Mendoza, Mariana, Prado-Garcia, Heriberto, Ordaz-Rosado, David, Avila, Euclides, Olmos-Ortiz, Andrea, López-Cisneros, Sofía, Larrea, Fernando, Díaz, Lorenza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896056/
https://www.ncbi.nlm.nih.gov/pubmed/31698751
http://dx.doi.org/10.3390/cancers11111739
_version_ 1783476696342593536
author García-Quiroz, Janice
García-Becerra, Rocío
Santos-Cuevas, Clara
Ramírez-Nava, Gerardo J.
Morales-Guadarrama, Gabriela
Cárdenas-Ochoa, Nohemí
Segovia-Mendoza, Mariana
Prado-Garcia, Heriberto
Ordaz-Rosado, David
Avila, Euclides
Olmos-Ortiz, Andrea
López-Cisneros, Sofía
Larrea, Fernando
Díaz, Lorenza
author_facet García-Quiroz, Janice
García-Becerra, Rocío
Santos-Cuevas, Clara
Ramírez-Nava, Gerardo J.
Morales-Guadarrama, Gabriela
Cárdenas-Ochoa, Nohemí
Segovia-Mendoza, Mariana
Prado-Garcia, Heriberto
Ordaz-Rosado, David
Avila, Euclides
Olmos-Ortiz, Andrea
López-Cisneros, Sofía
Larrea, Fernando
Díaz, Lorenza
author_sort García-Quiroz, Janice
collection PubMed
description Calcitriol is a multitarget anticancer hormone; however, its effects on angiogenesis remain contradictory. Herein, we tested whether the antiangiogenic phytochemicals curcumin or resveratrol improved calcitriol antitumorigenic effects in vivo. Triple-negative breast cancer tumoral cells (MBCDF-T) were xenografted in nude mice, maintaining treatments for 3 weeks. Tumor onset, volume and microvessel density were significantly reduced in mice coadministered with calcitriol and curcumin (Cal+Cur). Vessel count was also reduced in mice simultaneously treated with calcitriol and resveratrol (Cal+Rsv). Cal+Cur and Cal+Rsv treatments resulted in less tumor activated endothelium, as demonstrated by decreased tumor uptake of integrin-targeted biosensors in vivo. The renal gene expression of Cyp24a1 and Cyp27b1 suggested increased calcitriol bioactivity in the combined regimens. In vitro, the phytochemicals inhibited both MBCDF-T and endothelial cells proliferation, while potentiated calcitriol’s ability to reduce MBCDF-T cell-growth and endothelial cells migration. Resveratrol induced endothelial cell death, as deduced by increased sub-G1 cells accumulation, explaining the reduced tumor vessel number in resveratrol-treated mice, which further diminished when combined with calcitriol. In conclusion, the concomitant administration of calcitriol with curcumin or resveratrol synergistically promoted anticancer effects in vitro and in vivo in human mammary tumor cells. Whereas the results suggest different mechanisms of action of the phytochemicals when coadministered with calcitriol, the converging biological effect was inhibition of tumor neoangiogenesis.
format Online
Article
Text
id pubmed-6896056
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68960562019-12-23 Synergistic Antitumorigenic Activity of Calcitriol with Curcumin or Resveratrol is Mediated by Angiogenesis Inhibition in Triple Negative Breast Cancer Xenografts García-Quiroz, Janice García-Becerra, Rocío Santos-Cuevas, Clara Ramírez-Nava, Gerardo J. Morales-Guadarrama, Gabriela Cárdenas-Ochoa, Nohemí Segovia-Mendoza, Mariana Prado-Garcia, Heriberto Ordaz-Rosado, David Avila, Euclides Olmos-Ortiz, Andrea López-Cisneros, Sofía Larrea, Fernando Díaz, Lorenza Cancers (Basel) Article Calcitriol is a multitarget anticancer hormone; however, its effects on angiogenesis remain contradictory. Herein, we tested whether the antiangiogenic phytochemicals curcumin or resveratrol improved calcitriol antitumorigenic effects in vivo. Triple-negative breast cancer tumoral cells (MBCDF-T) were xenografted in nude mice, maintaining treatments for 3 weeks. Tumor onset, volume and microvessel density were significantly reduced in mice coadministered with calcitriol and curcumin (Cal+Cur). Vessel count was also reduced in mice simultaneously treated with calcitriol and resveratrol (Cal+Rsv). Cal+Cur and Cal+Rsv treatments resulted in less tumor activated endothelium, as demonstrated by decreased tumor uptake of integrin-targeted biosensors in vivo. The renal gene expression of Cyp24a1 and Cyp27b1 suggested increased calcitriol bioactivity in the combined regimens. In vitro, the phytochemicals inhibited both MBCDF-T and endothelial cells proliferation, while potentiated calcitriol’s ability to reduce MBCDF-T cell-growth and endothelial cells migration. Resveratrol induced endothelial cell death, as deduced by increased sub-G1 cells accumulation, explaining the reduced tumor vessel number in resveratrol-treated mice, which further diminished when combined with calcitriol. In conclusion, the concomitant administration of calcitriol with curcumin or resveratrol synergistically promoted anticancer effects in vitro and in vivo in human mammary tumor cells. Whereas the results suggest different mechanisms of action of the phytochemicals when coadministered with calcitriol, the converging biological effect was inhibition of tumor neoangiogenesis. MDPI 2019-11-06 /pmc/articles/PMC6896056/ /pubmed/31698751 http://dx.doi.org/10.3390/cancers11111739 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
García-Quiroz, Janice
García-Becerra, Rocío
Santos-Cuevas, Clara
Ramírez-Nava, Gerardo J.
Morales-Guadarrama, Gabriela
Cárdenas-Ochoa, Nohemí
Segovia-Mendoza, Mariana
Prado-Garcia, Heriberto
Ordaz-Rosado, David
Avila, Euclides
Olmos-Ortiz, Andrea
López-Cisneros, Sofía
Larrea, Fernando
Díaz, Lorenza
Synergistic Antitumorigenic Activity of Calcitriol with Curcumin or Resveratrol is Mediated by Angiogenesis Inhibition in Triple Negative Breast Cancer Xenografts
title Synergistic Antitumorigenic Activity of Calcitriol with Curcumin or Resveratrol is Mediated by Angiogenesis Inhibition in Triple Negative Breast Cancer Xenografts
title_full Synergistic Antitumorigenic Activity of Calcitriol with Curcumin or Resveratrol is Mediated by Angiogenesis Inhibition in Triple Negative Breast Cancer Xenografts
title_fullStr Synergistic Antitumorigenic Activity of Calcitriol with Curcumin or Resveratrol is Mediated by Angiogenesis Inhibition in Triple Negative Breast Cancer Xenografts
title_full_unstemmed Synergistic Antitumorigenic Activity of Calcitriol with Curcumin or Resveratrol is Mediated by Angiogenesis Inhibition in Triple Negative Breast Cancer Xenografts
title_short Synergistic Antitumorigenic Activity of Calcitriol with Curcumin or Resveratrol is Mediated by Angiogenesis Inhibition in Triple Negative Breast Cancer Xenografts
title_sort synergistic antitumorigenic activity of calcitriol with curcumin or resveratrol is mediated by angiogenesis inhibition in triple negative breast cancer xenografts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896056/
https://www.ncbi.nlm.nih.gov/pubmed/31698751
http://dx.doi.org/10.3390/cancers11111739
work_keys_str_mv AT garciaquirozjanice synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts
AT garciabecerrarocio synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts
AT santoscuevasclara synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts
AT ramireznavagerardoj synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts
AT moralesguadarramagabriela synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts
AT cardenasochoanohemi synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts
AT segoviamendozamariana synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts
AT pradogarciaheriberto synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts
AT ordazrosadodavid synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts
AT avilaeuclides synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts
AT olmosortizandrea synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts
AT lopezcisnerossofia synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts
AT larreafernando synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts
AT diazlorenza synergisticantitumorigenicactivityofcalcitriolwithcurcuminorresveratrolismediatedbyangiogenesisinhibitionintriplenegativebreastcancerxenografts