Anticancer Activities of the Quinone-Methide Triterpenes Maytenin and 22-β-hydroxymaytenin Obtained from Cultivated Maytenus ilicifolia Roots Associated with Down-Regulation of miRNA-27a and miR-20a/miR-17-5p

Autor: Camila Hernandes, Lucyene Miguita, Romario Oliveira de Sales, Elisangela de Paula Silva, Pedro Omori Ribeiro de Mendonça, Bruna Lorencini da Silva, Maria de Fatima Guarizo Klingbeil, Monica Beatriz Mathor, Erika Bevilaqua Rangel, Luciana Cavalheiro Marti, Juliana da Silva Coppede, Fabio Daumas Nunes, Ana Maria Soares Pereira, Patricia Severino
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Molecules, Vol 25, Iss 3, p 760 (2020)
Druh dokumentu: article
ISSN: 1420-3049
25030760
DOI: 10.3390/molecules25030760
Popis: 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-β-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-β-hydroxymaytenin in head and neck cancer cells indicates that these molecules should be further explored in plant biochemistry and biotechnology for therapeutic applications.
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