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

Autor(es):Mostrar menos -

Hernandes, Camila ^[1] ; Miguita, Lucyene ^[2] ; de Sales, Romario Oliveira ^[1] ; Silva, Elisangela de Paula ^[1] ; Ribeiro de Mendonca, Pedro Omori ^[1] ; da Silva, Bruna Lorencini ^[1] ; Guarizo Klingbeil, Maria de Fatima ^[3] ; Mathor, Monica Beatriz ^[3] ; Rangel, Erika Bevilaqua ^[1] ; Marti, Luciana Cavalheiro ^[1] ; Coppede, Juliana da Silva ^[4] ; Nunes, Fabio Daumas ^[2] ; Soares Pereira, Ana Maria ^[4] ; Severino, Patricia ^[1]

Afiliação do(s) autor(es)

^[1] Hosp Israelita Albert Einstein, Albert Einstein Res & Educ Inst, BR-05652900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Dent, Dept Stomatol, BR-05508000 Sao Paulo - Brazil

^[3] Nucl & Energy Res Inst IPEN CNEN SP, BR-05508000 Sao Paulo - Brazil

^[4] Univ Ribeirao Preto, Unidade Biotecnol, BR-14096900 Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecules; v. 25, n. 3 FEB 1 2020.
• Citações Web of Science: 0

Resumo

Natural triterpenes exhibit a wide range of biological activities. Since this group of secondary metabolites is structurally diverse, effects may vary due to distinct biochemical interactions within biological systems. In this work, we investigated the anticancer-related activities of the quinone-methide triterpene maytenin and its derivative compound 22-beta-hydroxymaytenin, obtained from Maytenus ilicifolia roots cultivated in vitro. Their antiproliferative and pro-apoptotic activities were evaluated in monolayer and three-dimensional cultures of immortalized cell lines. Additionally, we investigated the toxicity of maytenin in SCID mice harboring tumors derived from a squamous cell carcinoma cell line. Both isolated molecules presented pronounced pro-apoptotic activities in four cell lines derived from head and neck squamous cell carcinomas, including a metastasis-derived cell line. The molecules also induced reactive oxygen species (ROS) and down-regulated microRNA-27a and microRNA-20a/miR-17-5p, corroborating with the literature data for triterpenoids. Intraperitoneal administration of maytenin to tumor-bearing mice did not lead to pronounced histopathological changes in kidney tissue, suggesting low nephrotoxicity. The wide-ranging activity of maytenin and 22-beta-hydroxymaytenin in head and neck cancer cells indicates that these molecules should be further explored in plant biochemistry and biotechnology for therapeutic applications. (AU)

• Processo FAPESP: 15/11600-4 - Avaliação do potencial antineoplásico e mecanismos de ação de triterpenos isolados a partir de cultura de células de Maytenus ilicifolia
• Beneficiário: Patricia Severino
• Modalidade de apoio: Auxílio à Pesquisa - Regular