Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones
Sesquiterpene lactones (SLs) are abundant in plants and display a large spectrum of bioactivities. The compound britannin (BRT), found in different <i>Inula</i> species, is a pseudoguaianolide-type SL equipped with a typical and highly reactive α-methylene-γ-lactone moiety. The bioproper...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/10/1325 |
| _version_ | 1797515316471791616 |
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| author | Christian Bailly |
| author_facet | Christian Bailly |
| author_sort | Christian Bailly |
| collection | DOAJ |
| description | Sesquiterpene lactones (SLs) are abundant in plants and display a large spectrum of bioactivities. The compound britannin (BRT), found in different <i>Inula</i> species, is a pseudoguaianolide-type SL equipped with a typical and highly reactive α-methylene-γ-lactone moiety. The bioproperties of BRT and related pseudoguaianolide SLs, including helenalin, gaillardin, bigelovin and others, have been reviewed. Marked anticancer activities of BRT have been evidenced in vitro and in vivo with different tumor models. Three main mechanisms are implicated: (i) interference with the NFκB/ROS pathway, a mechanism common to many other SL monomers and dimers; (ii) blockade of the Keap1-Nrf2 pathway, with a covalent binding to a cysteine residue of Keap1 via the reactive α-methylene unit of BRT; (iii) a modulation of the c-Myc/HIF-1α signaling axis leading to a downregulation of the PD-1/PD-L1 immune checkpoint and activation of cytotoxic T lymphocytes. The non-specific reactivity of the α-methylene-γ-lactone moiety with the sulfhydryl groups of proteins is discussed. Options to reduce or abolish this reactivity have been proposed. Emphasis is placed on the capacity of BRT to modulate the tumor microenvironment and the immune-modulatory action of the natural product. The present review recapitulates the anticancer effects of BRT, some central concerns with SLs and discusses the implication of the PD1/PD-L1 checkpoint in its antitumor action. |
| first_indexed | 2024-03-10T06:43:47Z |
| format | Article |
| id | doaj.art-ca4f4289dae24e098340b56a7f01ba0a |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T06:43:47Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-ca4f4289dae24e098340b56a7f01ba0a2023-11-22T17:30:03ZengMDPI AGBiomedicines2227-90592021-09-01910132510.3390/biomedicines9101325Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene LactonesChristian Bailly0OncoWitan, Scientific Consulting Office, 59290 Lille, FranceSesquiterpene lactones (SLs) are abundant in plants and display a large spectrum of bioactivities. The compound britannin (BRT), found in different <i>Inula</i> species, is a pseudoguaianolide-type SL equipped with a typical and highly reactive α-methylene-γ-lactone moiety. The bioproperties of BRT and related pseudoguaianolide SLs, including helenalin, gaillardin, bigelovin and others, have been reviewed. Marked anticancer activities of BRT have been evidenced in vitro and in vivo with different tumor models. Three main mechanisms are implicated: (i) interference with the NFκB/ROS pathway, a mechanism common to many other SL monomers and dimers; (ii) blockade of the Keap1-Nrf2 pathway, with a covalent binding to a cysteine residue of Keap1 via the reactive α-methylene unit of BRT; (iii) a modulation of the c-Myc/HIF-1α signaling axis leading to a downregulation of the PD-1/PD-L1 immune checkpoint and activation of cytotoxic T lymphocytes. The non-specific reactivity of the α-methylene-γ-lactone moiety with the sulfhydryl groups of proteins is discussed. Options to reduce or abolish this reactivity have been proposed. Emphasis is placed on the capacity of BRT to modulate the tumor microenvironment and the immune-modulatory action of the natural product. The present review recapitulates the anticancer effects of BRT, some central concerns with SLs and discusses the implication of the PD1/PD-L1 checkpoint in its antitumor action.https://www.mdpi.com/2227-9059/9/10/1325britannincancer<i>Inula</i> speciesNFκBNrf2HIF-1α |
| spellingShingle | Christian Bailly Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones Biomedicines britannin cancer <i>Inula</i> species NFκB Nrf2 HIF-1α |
| title | Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones |
| title_full | Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones |
| title_fullStr | Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones |
| title_full_unstemmed | Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones |
| title_short | Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones |
| title_sort | anticancer targets and signaling pathways activated by britannin and related pseudoguaianolide sesquiterpene lactones |
| topic | britannin cancer <i>Inula</i> species NFκB Nrf2 HIF-1α |
| url | https://www.mdpi.com/2227-9059/9/10/1325 |
| work_keys_str_mv | AT christianbailly anticancertargetsandsignalingpathwaysactivatedbybritanninandrelatedpseudoguaianolidesesquiterpenelactones |