Antineoplastic potential and mechanisms of action of triterpenes isolated from cell culture of Maytenus ilicifolia

• Grant number: 15/11600-4
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2015
• End date: November 30, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Patricia Severino
• Grantee: Patricia Severino
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil
• Associated researchers: Ana Maria Soares Pereira ; Monica Beatriz Mathor ; WELBERT DE OLIVEIRA PEREIRA

Abstract

Maytenus ilicifolia has been used in traditional Brazilian medicine since the early 20's. The plant has numerous biological properties, and it is currently among the 12 species approved by the Sistema Único de Saúde, through its National Program of Medicinal Plants and Phytotherapeutics. The anticancer potential of M. ilicifolia is mostly studied for four quinonemethide triterpenes produced by its roots: celastrol, pristimerin, maytenin and 22-²-hydroximaytenin. However, the majority of the available studies were not carried out under controlled experimental conditions and focus on limited molecular aspects. A major difficulty for studies on the biological activity of these molecules is that the production is limited to the roots and at low concentration. This obstacle has been solved by the Biotechnology Department at UNAERP where a methodology for the production of the quinonemethide triterpenes from M. ilicifolia root cells cultivated in vitro was developed. This project aims at evaluating the effect of the four quinonemethide triterpenes on cell strains derived from head and neck squamous cell carcinomas (HNSCC) and in oral keratinocytes derived from primary cultures. HNSCC is one of the most common cancer types worldwide. It initiates on the epithelial lining of the oral cavity, pharynx and larynx, among other subsites, and it is mostly associated with tobacco and alcohol consumption. Most patients are diagnosed at advanced cancer stages and survival rates range 50% in 5 years. The molecular complexity of this cancer type is certainly the major drawback for the development of more efficient therapies. We will evaluate the effect of the triterpenes on cell proliferation and cell death and we will use gene expression microarrays in order to possibly understand the molecular mechanisms underlying the functional alterations observed. If promising results are found in the cell models, in vivo models will be used to further evaluate their potential efficacy for cancer treatment. We believe that the proposed methodology will contribute to the identification of targets for the four molecules evaluated here and will provide evidences for further studies on the possible application of M. ilicifolia-derived substances as auxiliary therapy for patients with HNSCC. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HERNANDES, CAMILA; SOARES PEREIRA, ANA MARIA; SEVERINO, PATRICIA. Compounds From Celastraceae Targeting Cancer Pathways and Their Potential Application in Head and Neck Squamous Cell Carcinoma: A Review. CURRENT GENOMICS, v. 18, n. 1, p. 60-74, 2017. (15/11600-4)

HERNANDES, CAMILA; MIGUITA, LUCYENE; DE SALES, ROMARIO OLIVEIRA; SILVA, ELISANGELA DE PAULA; RIBEIRO DE MENDONCA, PEDRO OMORI; DA SILVA, BRUNA LORENCINI; GUARIZO KLINGBEIL, MARIA DE FATIMA; MATHOR, MONICA BEATRIZ; RANGEL, ERIKA BEVILAQUA; MARTI, LUCIANA CAVALHEIRO; et al. Anticancer Activities of the Quinone-Methide Triterpenes Maytenin and 22-beta-hydroxymaytenin Obtained from Cultivated Maytenus ilicifolia Roots Associated with Down-Regulation of miRNA-27a and miR-20a/miR-17-5p. Molecules, v. 25, n. 3, FEB 1 2020. (15/11600-4)