Genome-Scale Metabolic Reconstruction, Non-Targeted LC-QTOF-MS Based Metabolomics Data, and Evaluation of Anticancer Activity of Cannabis sativa Leaf Extracts
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Published:2023-06-24
Issue:7
Volume:13
Page:788
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ISSN:2218-1989
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Container-title:Metabolites
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language:en
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Short-container-title:Metabolites
Author:
Camargo Fidias D. González12ORCID, Santamaria-Torres Mary3ORCID, Cala Mónica P.3ORCID, Guevara-Suarez Marcela2, Restrepo Silvia Restrepo4ORCID, Sánchez-Camargo Andrea1, Fernández-Niño Miguel5ORCID, Corujo María6, Gallo Molina Ada Carolina7, Cifuentes Javier8ORCID, Serna Julian A.8ORCID, Cruz Juan C.8ORCID, Muñoz-Camargo Carolina8ORCID, Gonzalez Barrios Andrés F.1ORCID
Affiliation:
1. Group of Product and Process Design, Department of Chemical and Food Engineering, Universidad de los Andes, Bogotá 111711, Colombia 2. Applied Genomics Research Group Vice-Presidency for Research and Creation, Universidad de los Andes, Bogotá 111711, Colombia 3. Metabolomics Core Facility—MetCore Vice-Presidency for Research and Creation, Universidad de los Andes, Bogotá 111711, Colombia 4. Laboratory of Mycology and Phytopathology (LAMFU), Department of Biological Sciences and Department of Chemical and Food Engineering, Universidad de los Andes, Bogotá 111711, Colombia 5. Leibniz-Institute of Plant Biochemistry, Department of Bioorganic Chemistry, Weinberg 3, 06110 Halle, Germany 6. Ecomedics S.A.S., Commercially Known as Clever Leaves, Calle 95 # 11A-94, Bogota 110221, Colombia 7. Chemical and Biochemical Processes Group, Department of Chemical and Environmental Engineering, National University of Colombia, Bogotá 11001, Colombia 8. Research Group on Nanobiomaterials, Cell Engineering and Bioprinting (GINIB), Department of Biomedical Engineering, Universidad de los Andes, Bogotá 111711, Colombia
Abstract
Over the past decades, Colombia has suffered complex social problems related to illicit crops, including forced displacement, violence, and environmental damage, among other consequences for vulnerable populations. Considerable effort has been made in the regulation of illicit crops, predominantly Cannabis sativa, leading to advances such as the legalization of medical cannabis and its derivatives, the improvement of crops, and leaving an open window to the development of scientific knowledge to explore alternative uses. It is estimated that C. sativa can produce approximately 750 specialized secondary metabolites. Some of the most relevant due to their anticancer properties, besides cannabinoids, are monoterpenes, sesquiterpenoids, triterpenoids, essential oils, flavonoids, and phenolic compounds. However, despite the increase in scientific research on the subject, it is necessary to study the primary and secondary metabolism of the plant and to identify key pathways that explore its great metabolic potential. For this purpose, a genome-scale metabolic reconstruction of C. sativa is described and contextualized using LC-QTOF-MS metabolic data obtained from the leaf extract from plants grown in the region of Pesca-Boyaca, Colombia under greenhouse conditions at the Clever Leaves facility. A compartmentalized model with 2101 reactions and 1314 metabolites highlights pathways associated with fatty acid biosynthesis, steroids, and amino acids, along with the metabolism of purine, pyrimidine, glucose, starch, and sucrose. Key metabolites were identified through metabolomic data, such as neurine, cannabisativine, cannflavin A, palmitoleic acid, cannabinoids, geranylhydroquinone, and steroids. They were analyzed and integrated into the reconstruction, and their potential applications are discussed. Cytotoxicity assays revealed high anticancer activity against gastric adenocarcinoma (AGS), melanoma cells (A375), and lung carcinoma cells (A549), combined with negligible impact against healthy human skin cells.
Funder
(CESED—Centro de Estudios sobre Seguridad y Drogas) of the School of Economics of the Universidad de los Andes, Bogotá Colombia
Subject
Molecular Biology,Biochemistry,Endocrinology, Diabetes and Metabolism
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