Erioflorin and Erioflorin Acetate Induce Cell Death in Advanced Prostate Cancer Through ROS Increase and NF-κB Inhibition
Germacranes are a type of sesquiterpene lactones with anti-inflammatory and cytotoxic properties against cancer cell lines. In this in vitro study, erioflorin and erioflorin acetate were isolated and purified from the leaves of <i>Podanthus mitiqui</i> Lindl (Mitique or Mitriu), a shrub...
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MDPI AG
2025-03-01
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| author | Cecilia Villegas Iván González-Chavarría Viviana Burgos Jaime R. Cabrera-Pardo Bernd Schmidt Cristian Paz |
| author_facet | Cecilia Villegas Iván González-Chavarría Viviana Burgos Jaime R. Cabrera-Pardo Bernd Schmidt Cristian Paz |
| author_sort | Cecilia Villegas |
| collection | DOAJ |
| description | Germacranes are a type of sesquiterpene lactones with anti-inflammatory and cytotoxic properties against cancer cell lines. In this in vitro study, erioflorin and erioflorin acetate were isolated and purified from the leaves of <i>Podanthus mitiqui</i> Lindl (Mitique or Mitriu), a shrub endemic to Chile and traditionally used in Mapuche medicine to treat urinary and digestive disorders. Their effects on advanced prostate cancer cell lines (DU-145 and 22Rv1) were evaluated. Cytotoxicity was assessed using real-time cell death and clonogenic assays. Apoptosis was determined by measuring reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and apoptotic cell percentage through flow cytometry. Gene expression of <i>BAX</i> and <i>BCL-2</i> was analyzed via RT-qPCR, while NF-κB activation was studied in DU-145 cells and human monocytic NF-κB reporter assays using LPS stimulation and alkaline phosphatase activity quantification. Erioflorin acetate exhibited the highest cytotoxicity, with IC<sub>50</sub> values of 35.1 µM (22Rv1) and 27.3 µM (DU-145), compared to erioflorin, which had IC<sub>50</sub> values of 50.3 µM and 56.5 µM, respectively. Both compounds increased ROS levels, reduced ΔΨm, and induced apoptosis. RT-qPCR analysis revealed that erioflorin elevated the <i>BAX/BCL-2</i> ratio, and both compounds inhibited NF-κB activation by preventing IκBα phosphorylation. In conclusion, the findings demonstrate that erioflorin and erioflorin acetate exert significant in vitro cytotoxic and cytostatic effects on prostate cancer cells, supporting their potential as natural candidates for prostate cancer therapy. |
| format | Article |
| id | doaj-art-32d4032a7457487c9dbca8eb86c4c32b |
| institution | DOAJ |
| issn | 2039-4705 2039-4713 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| series | Journal of Xenobiotics |
| spelling | doaj-art-32d4032a7457487c9dbca8eb86c4c32b2025-08-20T03:13:45ZengMDPI AGJournal of Xenobiotics2039-47052039-47132025-03-011524510.3390/jox15020045Erioflorin and Erioflorin Acetate Induce Cell Death in Advanced Prostate Cancer Through ROS Increase and NF-κB InhibitionCecilia Villegas0Iván González-Chavarría1Viviana Burgos2Jaime R. Cabrera-Pardo3Bernd Schmidt4Cristian Paz5Laboratory of Natural Products & Drug Discovery, Center CEBIM, Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, ChileDepartamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción 4070386, ChileEscuela de Tecnología Médica, Facultad de Salud, Universidad Santo Tomás, Temuco 4780000, ChileLaboratorio de Química Aplicada y Sustentable (LabQAS), Departamento de Química, Universidad del Bío-Bío, Avenida Collao 1202, Concepción 4051381, ChileInstitut für Chemie, Universität Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam, GermanyLaboratory of Natural Products & Drug Discovery, Center CEBIM, Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, ChileGermacranes are a type of sesquiterpene lactones with anti-inflammatory and cytotoxic properties against cancer cell lines. In this in vitro study, erioflorin and erioflorin acetate were isolated and purified from the leaves of <i>Podanthus mitiqui</i> Lindl (Mitique or Mitriu), a shrub endemic to Chile and traditionally used in Mapuche medicine to treat urinary and digestive disorders. Their effects on advanced prostate cancer cell lines (DU-145 and 22Rv1) were evaluated. Cytotoxicity was assessed using real-time cell death and clonogenic assays. Apoptosis was determined by measuring reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and apoptotic cell percentage through flow cytometry. Gene expression of <i>BAX</i> and <i>BCL-2</i> was analyzed via RT-qPCR, while NF-κB activation was studied in DU-145 cells and human monocytic NF-κB reporter assays using LPS stimulation and alkaline phosphatase activity quantification. Erioflorin acetate exhibited the highest cytotoxicity, with IC<sub>50</sub> values of 35.1 µM (22Rv1) and 27.3 µM (DU-145), compared to erioflorin, which had IC<sub>50</sub> values of 50.3 µM and 56.5 µM, respectively. Both compounds increased ROS levels, reduced ΔΨm, and induced apoptosis. RT-qPCR analysis revealed that erioflorin elevated the <i>BAX/BCL-2</i> ratio, and both compounds inhibited NF-κB activation by preventing IκBα phosphorylation. In conclusion, the findings demonstrate that erioflorin and erioflorin acetate exert significant in vitro cytotoxic and cytostatic effects on prostate cancer cells, supporting their potential as natural candidates for prostate cancer therapy.https://www.mdpi.com/2039-4713/15/2/45<i>Podanthus mitiqui</i>prostate cancererioflorinNF-κB signalingcytotoxicitygermacrane sesquiterpene lactones |
| spellingShingle | Cecilia Villegas Iván González-Chavarría Viviana Burgos Jaime R. Cabrera-Pardo Bernd Schmidt Cristian Paz Erioflorin and Erioflorin Acetate Induce Cell Death in Advanced Prostate Cancer Through ROS Increase and NF-κB Inhibition Journal of Xenobiotics <i>Podanthus mitiqui</i> prostate cancer erioflorin NF-κB signaling cytotoxicity germacrane sesquiterpene lactones |
| title | Erioflorin and Erioflorin Acetate Induce Cell Death in Advanced Prostate Cancer Through ROS Increase and NF-κB Inhibition |
| title_full | Erioflorin and Erioflorin Acetate Induce Cell Death in Advanced Prostate Cancer Through ROS Increase and NF-κB Inhibition |
| title_fullStr | Erioflorin and Erioflorin Acetate Induce Cell Death in Advanced Prostate Cancer Through ROS Increase and NF-κB Inhibition |
| title_full_unstemmed | Erioflorin and Erioflorin Acetate Induce Cell Death in Advanced Prostate Cancer Through ROS Increase and NF-κB Inhibition |
| title_short | Erioflorin and Erioflorin Acetate Induce Cell Death in Advanced Prostate Cancer Through ROS Increase and NF-κB Inhibition |
| title_sort | erioflorin and erioflorin acetate induce cell death in advanced prostate cancer through ros increase and nf κb inhibition |
| topic | <i>Podanthus mitiqui</i> prostate cancer erioflorin NF-κB signaling cytotoxicity germacrane sesquiterpene lactones |
| url | https://www.mdpi.com/2039-4713/15/2/45 |
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