Bioactive diterpenoid metabolism and cytotoxic activities of genetically transformed Euphorbia lathyris roots.
Identifieur interne : 000051 ( Main/Exploration ); précédent : 000050; suivant : 000052Bioactive diterpenoid metabolism and cytotoxic activities of genetically transformed Euphorbia lathyris roots.
Auteurs : Vincent A. Ricigliano [États-Unis] ; Vincent P. Sica [États-Unis] ; Sonja L. Knowles [États-Unis] ; Nicole Diette [États-Unis] ; Dianella G. Howarth [États-Unis] ; Nicholas H. Oberlies [États-Unis]Source :
- Phytochemistry [ 1873-3700 ] ; 2020.
Descripteurs français
- KwdFr :
- MESH :
- pharmacologie : Diterpènes.
- Euphorbia, Humains, Racines de plante.
English descriptors
- KwdEn :
- MESH :
- chemical , pharmacology : Diterpenes.
- Euphorbia, Humans, Plant Roots.
Abstract
Plants in the genus Euphorbia produce a wide variety of pharmacologically active diterpenoids with anticancer, multidrug resistance reversal, and antiviral properties. Some are the primary industrial source of ingenol mebutate, which is approved for treatment of the precancerous skin condition actinic keratosis. Similar to other high value phytochemicals, Euphorbia diterpenoids accumulate at low concentrations in planta and chemical synthesis produces similarly low yields. We established genetically transformed root cultures of Euphorbia lathryis as a strategy to gain greater access to diterpenoids from this genus. Transformed roots produced via stem explant infection with Agrobacterium rhizogenes strain 15834 recapitulated the metabolite profiles of field-grown plant roots and aerial tissues. Several putative diterpenoids were present in transformed roots, including ingenol and closely related structures, indicating that root cultures are a promising approach to Euphorbia-specific diterpenoid production. Treatment with methyl jasmonate led to a significant, albeit transient increase in mRNA levels of early diterpenoid biosynthetic enzymes (farnesyl pyrophosphate synthase, geranylgeranyl pyrophosphate synthase, and casbene synthase), suggesting that elicitation could prove useful in future pathway characterization and metabolic engineering efforts. We also show the potential of transformed E. lathyris root cultures for natural product drug discovery applications by measuring their cytotoxic activities using a panel of human carcinoma cell lines derived from prostate, cervix, breast, and lung.
DOI: 10.1016/j.phytochem.2020.112504
PubMed: 32980713
Affiliations:
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Howarth</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biological Sciences, St. John's University, Jamaica, NY, 11439, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biological Sciences, St. John's University, Jamaica, NY, 11439</wicri:regionArea><wicri:noRegion>11439</wicri:noRegion></affiliation></author><author><name sortKey="Oberlies, Nicholas H" sort="Oberlies, Nicholas H" uniqKey="Oberlies N" first="Nicholas H" last="Oberlies">Nicholas H. 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Some are the primary industrial source of ingenol mebutate, which is approved for treatment of the precancerous skin condition actinic keratosis. Similar to other high value phytochemicals, Euphorbia diterpenoids accumulate at low concentrations in planta and chemical synthesis produces similarly low yields. We established genetically transformed root cultures of Euphorbia lathryis as a strategy to gain greater access to diterpenoids from this genus. Transformed roots produced via stem explant infection with Agrobacterium rhizogenes strain 15834 recapitulated the metabolite profiles of field-grown plant roots and aerial tissues. Several putative diterpenoids were present in transformed roots, including ingenol and closely related structures, indicating that root cultures are a promising approach to Euphorbia-specific diterpenoid production. Treatment with methyl jasmonate led to a significant, albeit transient increase in mRNA levels of early diterpenoid biosynthetic enzymes (farnesyl pyrophosphate synthase, geranylgeranyl pyrophosphate synthase, and casbene synthase), suggesting that elicitation could prove useful in future pathway characterization and metabolic engineering efforts. We also show the potential of transformed E. lathyris root cultures for natural product drug discovery applications by measuring their cytotoxic activities using a panel of human carcinoma cell lines derived from prostate, cervix, breast, and lung.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" IndexingMethod="Automated" Owner="NLM"><PMID Version="1">32980713</PMID><DateCompleted><Year>2020</Year><Month>11</Month><Day>09</Day></DateCompleted><DateRevised><Year>2020</Year><Month>11</Month><Day>09</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-3700</ISSN><JournalIssue CitedMedium="Internet"><Volume>179</Volume><PubDate><Year>2020</Year><Month>Nov</Month></PubDate></JournalIssue><Title>Phytochemistry</Title><ISOAbbreviation>Phytochemistry</ISOAbbreviation></Journal><ArticleTitle>Bioactive diterpenoid metabolism and cytotoxic activities of genetically transformed Euphorbia lathyris roots.</ArticleTitle><Pagination><MedlinePgn>112504</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0031-9422(20)30740-8</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.phytochem.2020.112504</ELocationID><Abstract><AbstractText>Plants in the genus Euphorbia produce a wide variety of pharmacologically active diterpenoids with anticancer, multidrug resistance reversal, and antiviral properties. Some are the primary industrial source of ingenol mebutate, which is approved for treatment of the precancerous skin condition actinic keratosis. Similar to other high value phytochemicals, Euphorbia diterpenoids accumulate at low concentrations in planta and chemical synthesis produces similarly low yields. We established genetically transformed root cultures of Euphorbia lathryis as a strategy to gain greater access to diterpenoids from this genus. Transformed roots produced via stem explant infection with Agrobacterium rhizogenes strain 15834 recapitulated the metabolite profiles of field-grown plant roots and aerial tissues. Several putative diterpenoids were present in transformed roots, including ingenol and closely related structures, indicating that root cultures are a promising approach to Euphorbia-specific diterpenoid production. Treatment with methyl jasmonate led to a significant, albeit transient increase in mRNA levels of early diterpenoid biosynthetic enzymes (farnesyl pyrophosphate synthase, geranylgeranyl pyrophosphate synthase, and casbene synthase), suggesting that elicitation could prove useful in future pathway characterization and metabolic engineering efforts. We also show the potential of transformed E. lathyris root cultures for natural product drug discovery applications by measuring their cytotoxic activities using a panel of human carcinoma cell lines derived from prostate, cervix, breast, and lung.</AbstractText><CopyrightInformation>Published by Elsevier Ltd.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ricigliano</LastName><ForeName>Vincent A</ForeName><Initials>VA</Initials><AffiliationInfo><Affiliation>USDA-ARS, Honey Bee Breeding, Genetics and Physiology Research, Baton Rouge, LA, 70820, USA. Electronic address: Vincent.ricigliano@usda.gov.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sica</LastName><ForeName>Vincent P</ForeName><Initials>VP</Initials><AffiliationInfo><Affiliation>Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, 27402, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Knowles</LastName><ForeName>Sonja L</ForeName><Initials>SL</Initials><AffiliationInfo><Affiliation>Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, 27402, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Diette</LastName><ForeName>Nicole</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Dermatology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, 80227, USA; Charles C. Gates Center for Regenerative Medicine, Aurora, CO, 80227, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Howarth</LastName><ForeName>Dianella G</ForeName><Initials>DG</Initials><AffiliationInfo><Affiliation>Department of Biological Sciences, St. John's University, Jamaica, NY, 11439, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oberlies</LastName><ForeName>Nicholas H</ForeName><Initials>NH</Initials><AffiliationInfo><Affiliation>Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, 27402, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>09</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Phytochemistry</MedlineTA><NlmUniqueID>0151434</NlmUniqueID><ISSNLinking>0031-9422</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004224">Diterpenes</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D004224" MajorTopicYN="N">Diterpenes</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D028481" MajorTopicYN="Y">Euphorbia</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018517" MajorTopicYN="N">Plant Roots</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Agrobacterium</Keyword><Keyword MajorTopicYN="N">Anticancer</Keyword><Keyword MajorTopicYN="N">Diterpene</Keyword><Keyword MajorTopicYN="N">Euphorbia</Keyword><Keyword MajorTopicYN="N">Ingenol</Keyword><Keyword MajorTopicYN="N">Specialized metabolism</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>06</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>07</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>08</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>9</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>11</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>9</Month><Day>27</Day><Hour>20</Hour><Minute>31</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32980713</ArticleId><ArticleId IdType="pii">S0031-9422(20)30740-8</ArticleId><ArticleId IdType="doi">10.1016/j.phytochem.2020.112504</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Ricigliano, Vincent A" sort="Ricigliano, Vincent A" uniqKey="Ricigliano V" first="Vincent A" last="Ricigliano">Vincent A. Ricigliano</name></noRegion><name sortKey="Diette, Nicole" sort="Diette, Nicole" uniqKey="Diette N" first="Nicole" last="Diette">Nicole Diette</name><name sortKey="Howarth, Dianella G" sort="Howarth, Dianella G" uniqKey="Howarth D" first="Dianella G" last="Howarth">Dianella G. Howarth</name><name sortKey="Knowles, Sonja L" sort="Knowles, Sonja L" uniqKey="Knowles S" first="Sonja L" last="Knowles">Sonja L. Knowles</name><name sortKey="Oberlies, Nicholas H" sort="Oberlies, Nicholas H" uniqKey="Oberlies N" first="Nicholas H" last="Oberlies">Nicholas H. Oberlies</name><name sortKey="Sica, Vincent P" sort="Sica, Vincent P" uniqKey="Sica V" first="Vincent P" last="Sica">Vincent P. Sica</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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