4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references52

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Anticancer Molecular Mechanisms of Resveratrol

          Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Though it is only significantly present in grape products, a huge amount of preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Molecular mechanisms of resveratrol involved signaling pathways related to extracellular growth factors and receptor tyrosine kinases; formation of multiprotein complexes and cell metabolism; cell proliferation and genome instability; cytoplasmic tyrosine kinase signaling (cytokine, integrin, and developmental pathways); signal transduction by the transforming growth factor-β super-family; apoptosis and inflammation; and immune surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multidrug resistance: in adjuvant therapy, associated with 5-fluoruracyl and cisplatin, resveratrol had additive and/or synergistic effects increasing the chemosensitization of cancer cells. Resveratrol, by acting on diverse mechanisms simultaneously, has been emphasized as a promising, multi-target, anticancer agent, relevant in both cancer prevention and treatment.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Intratumor microvessel density as a prognostic factor in cancer.

            N Weidner (1995)
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Integrin alpha(v)beta(3)-Targeted Cancer Therapy.

              Anti-angiogenesis is a promising strategy for the treatment of cancer. Integrins, consisting of two noncovalently bound transmembrane alpha and beta subunits, are an important molecular family involved in tumor angiogenesis. The blockade of integrin signaling has been demonstrated to be efficient to inhibit tumor growth, angiogenesis, and metastasis. Among all the integrins, alpha(v)beta(3) seems to be the most important one during tumor angiogenesis. The inhibition of integrin alpha(v)beta(3) signaling with antibodies, peptides, peptidomimetics, and other antagonists has great potential in the treatment of cancer. In addition, integrin alpha(v)beta(3) is highly expressed on activated endothelial cells, new-born vessels as well as some tumor cells, but is not present in resting endothelial cells and most normal organ systems, making it a suitable target for anti-angiogenic therapy. In this article we will review the role of integrin alpha(v)beta(3) in angiogenesis, present recent progress in the use of integrin alpha(v)beta(3) antagonists and integrin-targeted delivery systems as potential cancer therapeutics, and discuss future perspectives.
                Bookmark

                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                06 November 2019
                November 2019
                : 11
                : 11
                : 1739
                Affiliations
                [1 ]Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Belisario Domínguez Sección XVI, Tlálpan 14080, Ciudad de México, Mexico rocio.garciab@ 123456iibiomedicas.unam.mx (R.G.-B.); gabriela.mguadarrama@ 123456gmail.com (G.M.-G.); cardenas9501@ 123456gmail.com (N.C.-O.); davo21_05@ 123456hotmail.com (D.O.-R.); euclides.avilac@ 123456incmnsz.mx (E.A.); biol.dslc@ 123456gmail.com (S.L.-C.); fernando.larreag@ 123456gmail.com (F.L.)
                [2 ]Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Av. Universidad 3000, Coyoacán 04510, Ciudad de México, Mexico
                [3 ]Departamento de Materiales Radiactivos, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Estado de México, Mexico; clara_letici@ 123456yahoo.com.mx (C.S.-C.); gerjul5420@ 123456hotmail.com (G.J.R.-N.)
                [4 ]Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Av. Universidad 3000, Coyoacán 04510, Ciudad de México, Mexico; monaco445@ 123456yahoo.com.mx
                [5 ]Departamento de Enfermedades Crónico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Belisario Domínguez Sección XVI, Tlalpan 14080, Ciudad de México, Mexico; hpradog@ 123456yahoo.com
                [6 ]Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Montes Urales 800, Lomas-Virreyes, Lomas de Chapultepec IV Sección, Miguel Hidalgo 11000, Ciudad de México, Mexico; nut.aolmos@ 123456gmail.com
                Author notes
                [* ]Correspondence: lorenzadiaz@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-2482-3963
                https://orcid.org/0000-0002-3128-1744
                https://orcid.org/0000-0002-4932-3244
                https://orcid.org/0000-0002-5456-9695
                https://orcid.org/0000-0002-5947-4222
                Article
                cancers-11-01739
                10.3390/cancers11111739
                6896056
                31698751
                c0407e91-15e4-4d1c-b1e8-2d4e3c6a3eed
                © 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/).

                History
                : 17 October 2019
                : 04 November 2019
                Categories
                Article

                angiogenesis,breast cancer,calcitriol,curcumin,resveratrol
                angiogenesis, breast cancer, calcitriol, curcumin, resveratrol

                Comments

                Comment on this article