Artesunate Inhibits the Growth Behavior of Docetaxel-Resistant Prostate Cancer Cells
Novel therapeutic strategies are urgently needed for advanced metastatic prostate cancer (PCa). Phytochemicals used in Traditional Chinese Medicine seem to exhibit tumor suppressive properties. Therefore, the therapeutic potential of artesunate (ART) on the progressive growth of therapy-sensitive (p...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.789284/full |
| _version_ | 1798024240612507648 |
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| author | Olesya Vakhrusheva Holger H. H. Erb Holger H. H. Erb Vitus Bräunig Sascha D. Markowitsch Patricia Schupp Patrick C. Baer Kimberly Sue Slade Anita Thomas Igor Tsaur Martin Puhr Zoran Culig Jindrich Cinatl Martin Michaelis Thomas Efferth Axel Haferkamp Eva Juengel |
| author_facet | Olesya Vakhrusheva Holger H. H. Erb Holger H. H. Erb Vitus Bräunig Sascha D. Markowitsch Patricia Schupp Patrick C. Baer Kimberly Sue Slade Anita Thomas Igor Tsaur Martin Puhr Zoran Culig Jindrich Cinatl Martin Michaelis Thomas Efferth Axel Haferkamp Eva Juengel |
| author_sort | Olesya Vakhrusheva |
| collection | DOAJ |
| description | Novel therapeutic strategies are urgently needed for advanced metastatic prostate cancer (PCa). Phytochemicals used in Traditional Chinese Medicine seem to exhibit tumor suppressive properties. Therefore, the therapeutic potential of artesunate (ART) on the progressive growth of therapy-sensitive (parental) and docetaxel (DX)-resistant PCa cells was investigated. Parental and DX-resistant PCa cell lines DU145, PC3, and LNCaP were incubated with artesunate (ART) [1-100 µM]. ART-untreated and ‘non-cancerous’ cells served as controls. Cell growth, proliferation, cell cycle progression, cell death and the expression of involved proteins were evaluated. ART, dose- and time-dependently, significantly restricted cell growth and proliferation of parental and DX-resistant PCa cells, but not of ‘normal, non-cancerous’ cells. ART-induced growth and proliferation inhibition was accompanied by G0/G1 phase arrest and down-regulation of cell cycle activating proteins in all DX-resistant PCa cells and parental LNCaP. In the parental and DX-resistant PC3 and LNCaP cell lines, ART also promoted apoptotic cell death. Ferroptosis was exclusively induced by ART in parental and DX-resistant DU145 cells by increasing reactive oxygen species (ROS). The anti-cancer activity displayed by ART took effect in all three PCa cell lines, but through different mechanisms of action. Thus, in advanced PCa, ART may hold promise as a complementary treatment together with conventional therapy. |
| first_indexed | 2024-04-11T17:59:13Z |
| format | Article |
| id | doaj.art-e8bf3189c0f242e381ae779a1a745f9c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T17:59:13Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e8bf3189c0f242e381ae779a1a745f9c2022-12-22T04:10:34ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-02-011210.3389/fonc.2022.789284789284Artesunate Inhibits the Growth Behavior of Docetaxel-Resistant Prostate Cancer CellsOlesya Vakhrusheva0Holger H. H. Erb1Holger H. H. Erb2Vitus Bräunig3Sascha D. Markowitsch4Patricia Schupp5Patrick C. Baer6Kimberly Sue Slade7Anita Thomas8Igor Tsaur9Martin Puhr10Zoran Culig11Jindrich Cinatl12Martin Michaelis13Thomas Efferth14Axel Haferkamp15Eva Juengel16Department of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, GermanyDepartment of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, GermanyDepartment of Urology, University of Dresden, Dresden, GermanyDepartment of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, GermanyDepartment of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, GermanyDepartment of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, GermanyDepartment of Internal Medicine III, Nephrology, University Hospital, Goethe-University, Frankfurt am Main, GermanyDepartment of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, GermanyDepartment of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, GermanyDepartment of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, GermanyDepartment of Urology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Urology, Medical University of Innsbruck, Innsbruck, AustriaInstitute of Medical Virology, Goethe-University, Frankfurt am Main, GermanyIndustrial Biotechnology Centre and School of Biosciences, University of Kent, Canterbury, United KingdomInstitute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Mainz, GermanyDepartment of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, GermanyDepartment of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, GermanyNovel therapeutic strategies are urgently needed for advanced metastatic prostate cancer (PCa). Phytochemicals used in Traditional Chinese Medicine seem to exhibit tumor suppressive properties. Therefore, the therapeutic potential of artesunate (ART) on the progressive growth of therapy-sensitive (parental) and docetaxel (DX)-resistant PCa cells was investigated. Parental and DX-resistant PCa cell lines DU145, PC3, and LNCaP were incubated with artesunate (ART) [1-100 µM]. ART-untreated and ‘non-cancerous’ cells served as controls. Cell growth, proliferation, cell cycle progression, cell death and the expression of involved proteins were evaluated. ART, dose- and time-dependently, significantly restricted cell growth and proliferation of parental and DX-resistant PCa cells, but not of ‘normal, non-cancerous’ cells. ART-induced growth and proliferation inhibition was accompanied by G0/G1 phase arrest and down-regulation of cell cycle activating proteins in all DX-resistant PCa cells and parental LNCaP. In the parental and DX-resistant PC3 and LNCaP cell lines, ART also promoted apoptotic cell death. Ferroptosis was exclusively induced by ART in parental and DX-resistant DU145 cells by increasing reactive oxygen species (ROS). The anti-cancer activity displayed by ART took effect in all three PCa cell lines, but through different mechanisms of action. Thus, in advanced PCa, ART may hold promise as a complementary treatment together with conventional therapy.https://www.frontiersin.org/articles/10.3389/fonc.2022.789284/fullprostate cancer (PCa)docetaxel (DX) resistanceartesunate (ART)Traditional Chinese Medicine (TCM)growth inhibitionapoptosis |
| spellingShingle | Olesya Vakhrusheva Holger H. H. Erb Holger H. H. Erb Vitus Bräunig Sascha D. Markowitsch Patricia Schupp Patrick C. Baer Kimberly Sue Slade Anita Thomas Igor Tsaur Martin Puhr Zoran Culig Jindrich Cinatl Martin Michaelis Thomas Efferth Axel Haferkamp Eva Juengel Artesunate Inhibits the Growth Behavior of Docetaxel-Resistant Prostate Cancer Cells Frontiers in Oncology prostate cancer (PCa) docetaxel (DX) resistance artesunate (ART) Traditional Chinese Medicine (TCM) growth inhibition apoptosis |
| title | Artesunate Inhibits the Growth Behavior of Docetaxel-Resistant Prostate Cancer Cells |
| title_full | Artesunate Inhibits the Growth Behavior of Docetaxel-Resistant Prostate Cancer Cells |
| title_fullStr | Artesunate Inhibits the Growth Behavior of Docetaxel-Resistant Prostate Cancer Cells |
| title_full_unstemmed | Artesunate Inhibits the Growth Behavior of Docetaxel-Resistant Prostate Cancer Cells |
| title_short | Artesunate Inhibits the Growth Behavior of Docetaxel-Resistant Prostate Cancer Cells |
| title_sort | artesunate inhibits the growth behavior of docetaxel resistant prostate cancer cells |
| topic | prostate cancer (PCa) docetaxel (DX) resistance artesunate (ART) Traditional Chinese Medicine (TCM) growth inhibition apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.789284/full |
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