Neolignans isolated from industrial hemp (Cannabis sativa L.) roots have cytotoxic effects on cancer cells

Abstract Background The 2018 Farm Bill states that cultivars of Cannabis sativa L. (industrial hemp) are legal for industrial use if total tetrahydrocannabinol (THC) concentrations are less than 0.30%. Due to this legislation, hemp cultivars with low total THC have found a wide range of uses, from a...

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Main Authors: Korey J. Brownstein, Grace E. Nieukirk, Jackson Edwards, Maria Thomas, Thu Hien Nguyen, Pedro A. de Alarcón, Karl E. Vermillion, Manu Gnanamony
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Journal of Cannabis Research
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Online Access:https://doi.org/10.1186/s42238-025-00316-5
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author Korey J. Brownstein
Grace E. Nieukirk
Jackson Edwards
Maria Thomas
Thu Hien Nguyen
Pedro A. de Alarcón
Karl E. Vermillion
Manu Gnanamony
author_facet Korey J. Brownstein
Grace E. Nieukirk
Jackson Edwards
Maria Thomas
Thu Hien Nguyen
Pedro A. de Alarcón
Karl E. Vermillion
Manu Gnanamony
author_sort Korey J. Brownstein
collection DOAJ
description Abstract Background The 2018 Farm Bill states that cultivars of Cannabis sativa L. (industrial hemp) are legal for industrial use if total tetrahydrocannabinol (THC) concentrations are less than 0.30%. Due to this legislation, hemp cultivars with low total THC have found a wide range of uses, from animal feed to paper production. Although cannabinoids are the most widely studied compounds in hemp, hemp produces numerous other compound classes as well, and these phytochemicals may have uses in the functional food and pharmaceutical industry. Methods Initial liquid chromatography profiling of hemp root samples revealed a group of uncharacterized peaks, and these peaks were tentatively identified as neolignans by Oribitrap ID-X high resolution mass spectrometer. To further elucidate the structure of these neolignans, we used techniques in liquid-liquid extraction, as well as flash chromatography to isolate them in preparation for NMR analysis. We then tested their inhibitory concentration 50 (IC50) in a variety of cancer cell lines. Results and discussion Four neolignans were isolated from hemp roots and each differed in their molecular weight by 30 daltons. Two of the compounds were identified as dadahols A and B. We tested fractions of various purities containing neolignans against neuroblastoma cell lines CHLA15 and LAN5, hepatoblastoma cell line Hep3B, and Hodgkin’s lymphoma cell line L428. We found that semi-pure fractions containing dadahol A and/or dadahol B had the highest cytotoxic activity. We then tested pure dadahol A and dadahol B, and this revealed dadahol A exhibited the lowest IC50 values in all the cell lines.
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spelling doaj-art-aa384582211049cfbcb9f543df334ac52025-08-20T03:06:51ZengBMCJournal of Cannabis Research2522-57822025-08-01711810.1186/s42238-025-00316-5Neolignans isolated from industrial hemp (Cannabis sativa L.) roots have cytotoxic effects on cancer cellsKorey J. Brownstein0Grace E. Nieukirk1Jackson Edwards2Maria Thomas3Thu Hien Nguyen4Pedro A. de Alarcón5Karl E. Vermillion6Manu Gnanamony7USDA, ARS, NCAUR, Functional Foods Research UnitU.S. Department of Energy, Oak Ridge Institute for Science and Education (ORISE) appointmentU.S. Department of Energy, Oak Ridge Institute for Science and Education (ORISE) appointmentDepartment of Pediatrics, University of Illinois College of Medicine PeoriaDepartment of Pediatrics, University of Illinois College of Medicine PeoriaDepartment of Pediatrics, University of Illinois College of Medicine PeoriaUSDA, ARS, NCAUR, Functional Foods Research UnitDepartment of Pediatrics, University of Illinois College of Medicine PeoriaAbstract Background The 2018 Farm Bill states that cultivars of Cannabis sativa L. (industrial hemp) are legal for industrial use if total tetrahydrocannabinol (THC) concentrations are less than 0.30%. Due to this legislation, hemp cultivars with low total THC have found a wide range of uses, from animal feed to paper production. Although cannabinoids are the most widely studied compounds in hemp, hemp produces numerous other compound classes as well, and these phytochemicals may have uses in the functional food and pharmaceutical industry. Methods Initial liquid chromatography profiling of hemp root samples revealed a group of uncharacterized peaks, and these peaks were tentatively identified as neolignans by Oribitrap ID-X high resolution mass spectrometer. To further elucidate the structure of these neolignans, we used techniques in liquid-liquid extraction, as well as flash chromatography to isolate them in preparation for NMR analysis. We then tested their inhibitory concentration 50 (IC50) in a variety of cancer cell lines. Results and discussion Four neolignans were isolated from hemp roots and each differed in their molecular weight by 30 daltons. Two of the compounds were identified as dadahols A and B. We tested fractions of various purities containing neolignans against neuroblastoma cell lines CHLA15 and LAN5, hepatoblastoma cell line Hep3B, and Hodgkin’s lymphoma cell line L428. We found that semi-pure fractions containing dadahol A and/or dadahol B had the highest cytotoxic activity. We then tested pure dadahol A and dadahol B, and this revealed dadahol A exhibited the lowest IC50 values in all the cell lines.https://doi.org/10.1186/s42238-025-00316-5Cannabis sativaIndustrial hempNeolignanRootPediatric cancer
spellingShingle Korey J. Brownstein
Grace E. Nieukirk
Jackson Edwards
Maria Thomas
Thu Hien Nguyen
Pedro A. de Alarcón
Karl E. Vermillion
Manu Gnanamony
Neolignans isolated from industrial hemp (Cannabis sativa L.) roots have cytotoxic effects on cancer cells
Journal of Cannabis Research
Cannabis sativa
Industrial hemp
Neolignan
Root
Pediatric cancer
title Neolignans isolated from industrial hemp (Cannabis sativa L.) roots have cytotoxic effects on cancer cells
title_full Neolignans isolated from industrial hemp (Cannabis sativa L.) roots have cytotoxic effects on cancer cells
title_fullStr Neolignans isolated from industrial hemp (Cannabis sativa L.) roots have cytotoxic effects on cancer cells
title_full_unstemmed Neolignans isolated from industrial hemp (Cannabis sativa L.) roots have cytotoxic effects on cancer cells
title_short Neolignans isolated from industrial hemp (Cannabis sativa L.) roots have cytotoxic effects on cancer cells
title_sort neolignans isolated from industrial hemp cannabis sativa l roots have cytotoxic effects on cancer cells
topic Cannabis sativa
Industrial hemp
Neolignan
Root
Pediatric cancer
url https://doi.org/10.1186/s42238-025-00316-5
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