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

**Authors:** Korey J. Brownstein, Grace E. Nieukirk, Jackson Edwards, Maria Thomas, Thu Hien Nguyen, Pedro A. de Alarcón, Karl E. Vermillion, Manu Gnanamony

PMC · DOI: 10.1186/s42238-025-00316-5 · Journal of Cannabis Research · 2025-08-16

## TL;DR

Researchers isolated neolignans from hemp roots and found they can kill cancer cells, with dadahol A being the most effective.

## Contribution

The study identifies and isolates new neolignans from hemp roots and evaluates their cytotoxic effects on cancer cells.

## Key findings

- Four neolignans were isolated from hemp roots, differing by 30 daltons in molecular weight.
- Dadahol A showed the lowest IC50 values across multiple cancer cell lines.
- Semi-pure fractions containing dadahol A and B had the highest cytotoxic activity.

## Abstract

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.

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.

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.

The online version contains supplementary material available at 10.1186/s42238-025-00316-5.

## Linked entities

- **Chemicals:** dadahol A (PubChem CID 636951), dadahol B (PubChem CID 11146784)
- **Diseases:** neuroblastoma (MONDO:0005072), hepatoblastoma (MONDO:0018666), Hodgkin’s lymphoma (MONDO:0004952)

## Full-text entities

- **Diseases:** liver cancer (MESH:D006528), necrosis (MESH:D009336), Hodgkin's lymphoma (MESH:D006689), neuroblastoma (MESH:D009447), inflammation (MESH:D007249), cancer (MESH:D009369), Cytotoxicity (MESH:D064420), hepatoblastoma (MESH:D018197)
- **Chemicals:** penicillin (MESH:D010406), Resazurin (MESH:C005843), B (MESH:D001895), Water (MESH:D014867), DMSO (MESH:D004121), acetic acid (MESH:D019342), methanol (MESH:D000432), streptomycin (MESH:D013307), cannabinoid (MESH:D002186), formic acid (MESH:C030544), flavonoids (MESH:D005419), THC (MESH:D013759), acetonitrile (MESH:C032159), tetramethylsilane (MESH:C073196), triterpenes (MESH:D014315), C (MESH:D002244), Ethyl acetate (MESH:C007650), DMEM (-), chloroform (MESH:D002725), CBD (MESH:D002185), CO2 (MESH:D002245), lignan (MESH:D017705)
- **Species:** Cannabis sativa (species) [taxon 3483], Cannabis (genus) [taxon 3482], Artocarpus dadah (species) [taxon 709041], Mycoplasma (genus) [taxon 2093]
- **Cell lines:** LAN5 — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0389), L428 — Homo sapiens (Human), Hodgkin lymphoma, Cancer cell line (CVCL_1361), CHLA15 — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_6594), Hep3B — Homo sapiens (Human), Childhood hepatocellular carcinoma, Cancer cell line (CVCL_0326)

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12357354