Cytotoxic and other bioactivities of a novel and known sesquiterpene lactones isolated from Vernonia leopoldi (Sch. Bip. ex Walp.) Vatke in breast cancer cell lines
Vernonia leopoldi (Sch. Bip. ex Walp.) Vatke (Asteraceae) is one of the widely used anti-cancer traditional medicinal plants in Ethiopia, despite the lack of data to support its therapeutic efficacy. Here we describe the isolation of compounds from the plant and the investigation of their cytotoxici...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Toxicology Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214750022000245 |
| _version_ | 1811295189066579968 |
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| author | Nigatu Tuasha Zilma Escobar Daniel Seifu Endalamaw Gadisa Beyene Petros Olov Sterner Stina Oredsson |
| author_facet | Nigatu Tuasha Zilma Escobar Daniel Seifu Endalamaw Gadisa Beyene Petros Olov Sterner Stina Oredsson |
| author_sort | Nigatu Tuasha |
| collection | DOAJ |
| description | Vernonia leopoldi (Sch. Bip. ex Walp.) Vatke (Asteraceae) is one of the widely used anti-cancer traditional medicinal plants in Ethiopia, despite the lack of data to support its therapeutic efficacy. Here we describe the isolation of compounds from the plant and the investigation of their cytotoxicity and other bioactivities. We identified the novel sesquiterpene lactone (SL) 11ß,13-dihydrovernodalol along with the three other SLs (vernomenin, vernolepin, and 11ß,13-dihydrovernodalin) and three flavonoids (apigenin, eriodyctiol, and luteolin) isolated from this plant for the first time. The structures of all the compounds were established based on extensive analysis of nuclear magnetic resonance spectroscopic data and confirmed by high-resolution electrospray ionization mass spectrometry. We then studied the biological activities of the SLs and found that all were cytotoxic at low μM ranges against MCF-7 and JIMT-1 breast cancer cells as well as against the normal-like MCF-10A breast epithelial cells evaluated in a spectrophotometric assay. All the SLs significantly reduced JIMT-1 cell migration after 72 h of treatment with 2 μM concentrations in a wound healing assay. Treatment with all SLs reduced the aldehyde dehydrogenase expressing cancer stem cell sub-population of the JIMT-1 cells significantly, evaluated by flow cytometry. Only 11ß,13-dihydrovernodalin resulted in a significant inhibition of tumor necrosis factor-α-induced translocation of nuclear factor κB to the cell nucleus. In addition, we show that the reporter fluorophore nitrobenzoxadiazole (NBD) can successfully be conjugated with an SL and that this SL-NBD conjugate is taken up efficiently in JIMT-1 cells. Therefore, the overall bioactivities of the SL compounds and specifically their effects against the stemness of breast cancer cells make them prime candidates for further in-depth investigation. |
| first_indexed | 2024-04-13T05:28:49Z |
| format | Article |
| id | doaj.art-ad51a5f8e0534a87b2e68460615caa41 |
| institution | Directory Open Access Journal |
| issn | 2214-7500 |
| language | English |
| last_indexed | 2024-04-13T05:28:49Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj.art-ad51a5f8e0534a87b2e68460615caa412022-12-22T03:00:30ZengElsevierToxicology Reports2214-75002022-01-019382392Cytotoxic and other bioactivities of a novel and known sesquiterpene lactones isolated from Vernonia leopoldi (Sch. Bip. ex Walp.) Vatke in breast cancer cell linesNigatu Tuasha0Zilma Escobar1Daniel Seifu2Endalamaw Gadisa3Beyene Petros4Olov Sterner5Stina Oredsson6Department of Biology, Hawassa College of Teacher Education, Hawassa, Sidaama National Regional State, Ethiopia; Department of Microbial, Cellular and Molecular Biology, College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Department of Biology, Faculty of Natural Science, Lund University, Lund, SwedenCentre for Analysis and Synthesis, Faculty of Science, Lund University, Lund, SwedenDepartment of Biochemistry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, EthiopiaArmauer Hansen Research Institute (AHRI), Addis Ababa, EthiopiaDepartment of Microbial, Cellular and Molecular Biology, College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa, EthiopiaCentre for Analysis and Synthesis, Faculty of Science, Lund University, Lund, SwedenDepartment of Biology, Faculty of Natural Science, Lund University, Lund, Sweden; Corresponding author.Vernonia leopoldi (Sch. Bip. ex Walp.) Vatke (Asteraceae) is one of the widely used anti-cancer traditional medicinal plants in Ethiopia, despite the lack of data to support its therapeutic efficacy. Here we describe the isolation of compounds from the plant and the investigation of their cytotoxicity and other bioactivities. We identified the novel sesquiterpene lactone (SL) 11ß,13-dihydrovernodalol along with the three other SLs (vernomenin, vernolepin, and 11ß,13-dihydrovernodalin) and three flavonoids (apigenin, eriodyctiol, and luteolin) isolated from this plant for the first time. The structures of all the compounds were established based on extensive analysis of nuclear magnetic resonance spectroscopic data and confirmed by high-resolution electrospray ionization mass spectrometry. We then studied the biological activities of the SLs and found that all were cytotoxic at low μM ranges against MCF-7 and JIMT-1 breast cancer cells as well as against the normal-like MCF-10A breast epithelial cells evaluated in a spectrophotometric assay. All the SLs significantly reduced JIMT-1 cell migration after 72 h of treatment with 2 μM concentrations in a wound healing assay. Treatment with all SLs reduced the aldehyde dehydrogenase expressing cancer stem cell sub-population of the JIMT-1 cells significantly, evaluated by flow cytometry. Only 11ß,13-dihydrovernodalin resulted in a significant inhibition of tumor necrosis factor-α-induced translocation of nuclear factor κB to the cell nucleus. In addition, we show that the reporter fluorophore nitrobenzoxadiazole (NBD) can successfully be conjugated with an SL and that this SL-NBD conjugate is taken up efficiently in JIMT-1 cells. Therefore, the overall bioactivities of the SL compounds and specifically their effects against the stemness of breast cancer cells make them prime candidates for further in-depth investigation.http://www.sciencedirect.com/science/article/pii/S2214750022000245Vernonia leopoldiTraditional medicineIsolation of anti-cancer bioactive compoundsNovel sesquiterpene lactoneCancer stem cells |
| spellingShingle | Nigatu Tuasha Zilma Escobar Daniel Seifu Endalamaw Gadisa Beyene Petros Olov Sterner Stina Oredsson Cytotoxic and other bioactivities of a novel and known sesquiterpene lactones isolated from Vernonia leopoldi (Sch. Bip. ex Walp.) Vatke in breast cancer cell lines Toxicology Reports Vernonia leopoldi Traditional medicine Isolation of anti-cancer bioactive compounds Novel sesquiterpene lactone Cancer stem cells |
| title | Cytotoxic and other bioactivities of a novel and known sesquiterpene lactones isolated from Vernonia leopoldi (Sch. Bip. ex Walp.) Vatke in breast cancer cell lines |
| title_full | Cytotoxic and other bioactivities of a novel and known sesquiterpene lactones isolated from Vernonia leopoldi (Sch. Bip. ex Walp.) Vatke in breast cancer cell lines |
| title_fullStr | Cytotoxic and other bioactivities of a novel and known sesquiterpene lactones isolated from Vernonia leopoldi (Sch. Bip. ex Walp.) Vatke in breast cancer cell lines |
| title_full_unstemmed | Cytotoxic and other bioactivities of a novel and known sesquiterpene lactones isolated from Vernonia leopoldi (Sch. Bip. ex Walp.) Vatke in breast cancer cell lines |
| title_short | Cytotoxic and other bioactivities of a novel and known sesquiterpene lactones isolated from Vernonia leopoldi (Sch. Bip. ex Walp.) Vatke in breast cancer cell lines |
| title_sort | cytotoxic and other bioactivities of a novel and known sesquiterpene lactones isolated from vernonia leopoldi sch bip ex walp vatke in breast cancer cell lines |
| topic | Vernonia leopoldi Traditional medicine Isolation of anti-cancer bioactive compounds Novel sesquiterpene lactone Cancer stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S2214750022000245 |
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