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Matteucinol, isolated from Miconia chamissois, induces apoptosis in human glioblastoma lines via the intrinsic pathway and inhibits angiogenesis and tumor growth in vivo

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Summary

Gliomas account for nearly 70% of the central nervous system tumors and present a median survival of approximately 12–17 months. Studies have shown that administration of novel natural antineoplastic agents is been highly effective for treating gliomas. This study was conducted to investigate the antitumor potential (in vitro and in vivo) of Miconia chamissois Naudin for treating glioblastomas. We investigated the cytotoxicity of the chloroform partition and its sub-fraction in glioblastoma cell lines (GAMG and U251MG) and one normal cell line of astrocytes. The fraction showed cytotoxicity and was selective for tumor cells. Characterization of this fraction revealed a single compound, Matteucinol, which was first identified in the species M. chamissois. Matteucinol promoted cell death via intrinsic apoptosis in the adult glioblastoma lines. In addition, Matteucinol significantly reduced the migration, invasion, and clonogenicity of the tumor cells. Notably, it also reduced tumor growth and angiogenesis in vivo. Moreover, this agent showed synergistic effects with temozolomide, a chemotherapeutic agent commonly used in clinical practice. Our study demonstrates that Matteucinol from M chamissois is a promising compound for the treatment of glioblastomas and may be used along with the existing chemotherapeutic agents for more effective treatment.

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Funding

The work was supported by Minas Gerais State Research Foundation (FAPEMIG), National Council for Scientific and Technological Development (CNPq),and supported partially by grantsfrom the FINEP (MCTI/ FINEP/MS/SCTIE/DECIT-01/2013 - FPXII-BIOPLAT). This work was conducted during a scholarship supported by the International Cooperation Program CAPES (Brazilian Federal Agency for Support and Evaluation of Graduate Education within the Ministry of Education of Brazil) at the Federal University of São João del Rei.

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Authors and Affiliations

  1. Experimental Pathology Laboratory, Federal University of São João del Rei, 400, Sebastião Gonçalves Coelho- Chanadour, Divinópolis, MG, 35501-296, Brazil

    Ana Gabriela Silva, Rafael César Russo Chagas & Rosy Iara Maciel de Azambuja Ribeiro

  2. Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, 14784-400, Brazil

    Viviane Aline O. Silva, Renato J. S. Oliveira & Rui Manuel Reis

  3. State University of Minas Gerais, Ituiutaba, MG, 38302-192, Brazil

    Allisson Rodrigues de Rezende

  4. Department of Chemistry, Institute of Exact Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-90, Brazil

    Lúcia Pinheiro Santos Pimenta

  5. Petroleomic and Forensic Laboratory, Chemistry Department, Federal University of Espírito Santo, Vitória, ES, 29075-910, Brazil

    Wanderson Romão

  6. Federal Institute of Education, Science and Technology of Espírito Santo, Vila Velha, ES, 29106-010, Brazil

    Wanderson Romão

  7. Tissue Processing Laboratory, Federal University of São João del Rei (UFSJ), 400, Sebastião Gonçalves Coelho, Chanadour, Divinópolis, MG, Brazil

    Hélio Batista Santos & Ralph Gruppi Thomé

  8. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

    Rui Manuel Reis

  9. ICVS/3B’s - PT Government Associate Laboratory, 4806909, Braga/Guimarães, Portugal

    Rui Manuel Reis

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  1. Ana Gabriela Silva
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Correspondence to Rui Manuel Reis or Rosy Iara Maciel de Azambuja Ribeiro.

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Conflict of interest

Author Silva, A.G. declares that she has no conflict of interest. Author Saito, V.A.O.S. declares that she has no conflict of interest. Author Oliveira R.J.S. declares that he has no conflict of interest. Author Rezende, A.R. declares that he has no conflict of interest. Author Chagas R.C.R. declares that he has no conflict of interest. Author Pimenta, L.P.S. declares that she has no conflict of interest. Author Romão, W. declares that he has no conflict of interest. Author Santos, H.B. declares that he has no conflict of interest. Author Thomé R.G. declares that he has no conflict of interest. Author Reis, R. declares that he has no conflict of interest. Author Ribeiro, R.I.M.A. declares that she has no conflict of interest.

Ethical approval

This article has a study with animals, ethical approval was obtained by the Ethics Committee of the Foundation Pio XII IRCAD Brazil under protocol number 027/2016. All applicable international, national, institutional guidelines for the care and use of animals were followed.

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Silva, A.G., Silva, V.A.O., Oliveira, R.J.S. et al. Matteucinol, isolated from Miconia chamissois, induces apoptosis in human glioblastoma lines via the intrinsic pathway and inhibits angiogenesis and tumor growth in vivo. Invest New Drugs 38, 1044–1055 (2020). https://doi.org/10.1007/s10637-019-00878-1

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