| Autor: |
Nigatu Tuasha, Zilma Escobar, Daniel Seifu, Endalamaw Gadisa, Beyene Petros, Olov Sterner, Stina Oredsson |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Toxicology Reports, Vol 9, Iss , Pp 382-392 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2214-7500 |
| DOI: |
10.1016/j.toxrep.2022.02.011 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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