Bioactive diterpenoid metabolism and cytotoxic activities of genetically transformed Euphorbia lathyris roots

Ricigliano, Vincent A.; Sica, Vincent P.; Knowles, Sonja L.; Diette, N.; Howarth, Dianella G.; Oberlies, Nicholas H.

doi:10.1016/j.phytochem.2020.112504

Cited by 9 publications

(7 citation statements)

References 50 publications

(63 reference statements)

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“…Furthermore, this overestimation is also likely to be of equal magnitude across all species and organs and therefore, will not have a significant impact on the general conclusions of our study. Regarding terminology, these 1,311 features meet or exceed the level of curation beyond which features have, for clarity, been described as "compounds" in the chemical ecology literature (e.g., Sedio et al, 2017;Schneider et al, 2019;Christian et al, 2020;Ricigliano et al, 2020). Thus, for the sake of consistency and clarity, we refer to our curated features as compounds.…”

Section: Untargeted Metabolomics and Molecular Networking Reveal High Chemical Diversity And Many Compounds Unique To Fruitsmentioning

confidence: 99%

Comparative Metabolomics of Fruits and Leaves in a Hyperdiverse Lineage Suggests Fruits Are a Key Incubator of Phytochemical Diversification

et al. 2021

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Interactions between plants and leaf herbivores have long been implicated as the major driver of plant secondary metabolite diversity. However, other plant-animal interactions, such as those between fruits and frugivores, may also be involved in phytochemical diversification. Using 12 species of Piper, we conducted untargeted metabolomics and molecular networking with extracts of fruits and leaves. We evaluated organ-specific secondary metabolite composition and compared multiple dimensions of phytochemical diversity across organs, including richness, structural complexity, and variability across samples at multiple scales within and across species. Plant organ identity, species identity, and the interaction between the two all significantly influenced secondary metabolite composition. Leaves and fruit shared a majority of compounds, but fruits contained more unique compounds and had higher total estimated chemical richness. While the relative levels of chemical richness and structural complexity across organs varied substantially across species, fruit diversity exceeded leaf diversity in more species than the reverse. Furthermore, the variance in chemical composition across samples was higher for fruits than leaves. By documenting a broad pattern of high phytochemical diversity in fruits relative to leaves, this study lays groundwork for incorporating fruit into a comprehensive and integrative understanding of the ecological and evolutionary factors shaping secondary metabolite composition at the whole-plant level.

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Section: Untargeted Metabolomics and Molecular Networking Reveal High Chemical Diversity And Many Compounds Unique To Fruitsmentioning

confidence: 99%

Comparative Metabolomics of Fruits and Leaves in a Hyperdiverse Lineage Suggests Fruits Are a Key Incubator of Phytochemical Diversification

et al. 2021

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“…Elucidating the biosynthetic pathway of ingenol mebutate and other diterpenoids of medical relevance is a research priority in Euphorbia(Bergman et al 2019; Ricigliano et al 2020; Forestier et al 2021) . Ingenol mebutate has a 5/7/7/3 carbon ring system.…”

Section: Resultsmentioning

confidence: 99%

Chromosome-level genome assembly ofEuphorbia peplus, a model system for plant latex, reveals that relative lack of Ty3 transposons contributed to its small genome size

Johnson

Yue

Carey

et al. 2022

Preprint

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Euphorbia peplus (petty spurge) is a small, fast-growing plant that is native to Eurasia and has become a naturalized weed in North America and Australia. E. peplus is not only medicinally valuable, serving as a source for the skin cancer drug ingenol mebutate, but also has great potential as a model for latex production owing to its small size, ease of manipulation in the laboratory, and rapid reproductive cycle. To help establish E. peplus as a new model, we generated a 267.2 Mb HiC-anchored PacBio HiFi nuclear genome assembly with an embryophyta BUSCO score of 98.5%, a genome annotation based on RNA-seq data from six tissues, and publicly accessible tools including a genome browser and an interactive organ-specific expression atlas. Chromosome number is highly variable across Euphorbia species. Using a comparative analysis of our newly sequenced E. peplus genome with other Euphorbiaceae genomes, we show that variation in Euphorbia chromosome number is likely due to fragmentation and rearrangement rather than aneuploidy. Moreover, we found that the E. peplus genome is relatively compact compared to related members of the genus in part due to restricted expansion of the Ty3 transposon family. Finally, we identify a large gene cluster that contains many previously identified enzymes in the putative ingenol mebutate biosynthesis pathway, along with additional gene candidates for this biosynthetic pathway. The genomic resources we have created for E. peplus will help advance research on latex production and ingenol mebutate biosynthesis in the commercially important Euphorbiaceae family.

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“…Furthermore, Euphorbia roots also contain diterpenoids with biological activity [8,40,41]. In fact, the roots of Euphorbia lathyris have been recently described as a new source of Euphorbia biomolecules that may show additional benefits [42]. We applied a defatting process to the mature seeds of Euphorbia lathyris (variety S3201), not only to increase the concentration of polyphenols with high bioactive capacity in the seed flour, but also to avoid interferences in the extraction process caused by the high fat content of Euphorbia seeds, thus ensuring a high extraction yield.…”

Section: Discussionmentioning

confidence: 99%

Antitumor Effect of the Ethanolic Extract from Seeds of Euphorbia lathyris in Colorectal Cancer

et al. 2021

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The seeds of Euphorbia lathyris have been used in traditional medicine to treat various medical conditions. However, neither all of their active biocompounds nor the molecular mechanisms underlying their therapeutic effects have been described. A new ethanolic extract of defatted flour from mature seeds of Euphorbia lathyris showed a high total polyphenol content and significant antioxidant activity. Chromatographic analysis showed that esculetin, euphorbetin, gaultherin, and kaempferol-3-rutinoside were the most abundant polyphenolic bioactive compounds. Antiproliferative assays showed a high and selective antitumor activity against colon cancer cell lines (T84 and HCT-15). In addition, a significant antiproliferative activity against glioblastoma multiforme cells was also demonstrated. Its mechanism of action to induce cell death was mediated by the overexpression of caspases 9, 3, and 8, and by activation of autophagy. Interestingly, a reduction in the migration capacity of colon cancer cells and a significant antiangiogenic effect on human umbilical vein endothelial cells were also demonstrated. Finally, the extract significantly reduced the subpopulations of cancer stem cells. This extract could be the basis to develop new therapeutic strategies for the treatment of colon cancer, although further experiments will be necessary to determine its in vivo effects.

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Bioactive diterpenoid metabolism and cytotoxic activities of genetically transformed Euphorbia lathyris roots

Cited by 9 publications

References 50 publications

Comparative Metabolomics of Fruits and Leaves in a Hyperdiverse Lineage Suggests Fruits Are a Key Incubator of Phytochemical Diversification

Comparative Metabolomics of Fruits and Leaves in a Hyperdiverse Lineage Suggests Fruits Are a Key Incubator of Phytochemical Diversification

Chromosome-level genome assembly ofEuphorbia peplus, a model system for plant latex, reveals that relative lack of Ty3 transposons contributed to its small genome size

Antitumor Effect of the Ethanolic Extract from Seeds of Euphorbia lathyris in Colorectal Cancer

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