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

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-me...

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Bibliographic Details
Published in:	Molecules (Basel, Switzerland) Vol. 25; no. 3; p. 760
Main Authors:	Hernandes, Camila, Miguita, Lucyene, de Sales, Romario Oliveira, Silva, Elisangela de Paula, Mendonça, Pedro Omori Ribeiro de, Lorencini da Silva, Bruna, Klingbeil, Maria de Fatima Guarizo, Mathor, Monica Beatriz, Rangel, Erika Bevilaqua, Marti, Luciana Cavalheiro, Coppede, Juliana da Silva, Nunes, Fabio Daumas, Pereira, Ana Maria Soares, Severino, Patricia
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 10-02-2020 MDPI
Subjects:	Acute Kidney Injury - chemically induced Animals Antineoplastic Agents, Phytogenic - adverse effects Antineoplastic Agents, Phytogenic - chemistry Antineoplastic Agents, Phytogenic - pharmacology Apoptosis Apoptosis - drug effects Biotechnology Cancer therapies Cell culture Cell growth Cell Line, Tumor Cytotoxicity Deoxyribonucleic acid DNA Down-Regulation - drug effects Drug Screening Assays, Antitumor Female Gene expression Gene Expression Regulation, Neoplastic - drug effects Head and Neck Neoplasms - drug therapy Head and Neck Neoplasms - genetics Head and Neck Neoplasms - pathology Humans Investigations Keratinocytes - drug effects Maytenus Maytenus - chemistry Metabolites Metastases Metastasis Mice, SCID microrna MicroRNAs MicroRNAs - genetics miRNA Oxidative stress Plant Extracts - chemistry Plant Roots - chemistry quinone-methide Quinones Roots Secondary metabolites Spheroids Squamous cell carcinoma Squamous Cell Carcinoma of Head and Neck - drug therapy Squamous Cell Carcinoma of Head and Neck - genetics Squamous Cell Carcinoma of Head and Neck - pathology Therapeutic applications Toxicity triterpene Triterpenes Triterpenes - adverse effects Triterpenes - chemistry Triterpenes - pharmacology Triterpenoids Tumors Xenograft Model Antitumor Assays triterpene microRNA quinone-methide squamous cell carcinoma
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Summary:	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 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.
ISSN:	1420-3049 1420-3049
DOI:	10.3390/molecules25030760