2. Academic Validation
  3. Novel merosesquiterpene exerts a potent antitumor activity against breast cancer cells in vitro and in vivo

Novel merosesquiterpene exerts a potent antitumor activity against breast cancer cells in vitro and in vivo

  • Eur J Med Chem. 2014 May 22:79:1-12. doi: 10.1016/j.ejmech.2014.03.071.
Esther Carrasco 1,  Pablo Juan Álvarez 2,  Consolación Melguizo 2,  José Prados 2,  Enrique Álvarez-Manzaneda 3,  Rachid Chahboun 3,  Ibtissam Messouri 3,  María Isabel Vázquez-Vázquez 2,  Antonia Aránega 2,  Fernando Rodríguez-Serrano 4
Affiliations

Affiliations

  • 1 Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, 18071 Granada, Spain; PhD Program in Biomedicine, University of Granada, 18071 Granada, Spain.
  • 2 Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, 18071 Granada, Spain.
  • 3 Department of Organic Chemistry, Institute of Biotechnology, University of Granada, 18071 Granada, Spain.
  • 4 Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, 18071 Granada, Spain. Electronic address: fernrs@ugr.es.
PMID: 24704691 DOI: 10.1016/j.ejmech.2014.03.071
Abstract

This article describes the antitumor properties of a new family of merosesquiterpenes, which were synthesized by Diels-Alder cycloaddition of the labdane diene trans-communic acid, highly abundant in Cupressus sempervirens, or its methyl ester, with the appropriate dienophile. These compounds demonstrated potent cytotoxic activity in vitro against human breast, colon, and lung tumor cells. We highlight the elevated activity (IC50: 0.35 ± 0.10 μM) and specificity (TI: 9) of compound 13 against the MCF-7 line, which corresponds to the most prevalent breast Cancer cell subtype, luminal A. It was found that compound 13 exerts its anti-tumor action by inducing oxidative stress, arresting the cell cycle in stages G0-G1, and activating Apoptosis, which are all associated with low cyclin D1 regulation, pRb hypophosphorylation, increased expression of p27 and p53, and poly (ADP-ribose) polymerase (PARP) fractioning. Epithelial-mesenchymal transition, a phenomenon associated with metastasis promotion and a worsened prognosis also appeared to be inhibited by compound 13. In addition, it markedly reduced tumor development in immunocompetent C57BL/6 mice with allografts of E0771 mouse breast tumor cells (luminal A subtype). According to these findings, this new family of compounds, especially compound 13, may be highly useful in the treatment of human breast Cancer.

Keywords

Allografts; Apoptosis; Cancer; Cell cycle arrest; Merosesquiterpene; Oxidative stress.

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