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Autoren: Markowitsch, Sascha D.
Juetter, Kira M.
Schupp, Patricia
Hauschulte, Kristine
Vakhrusheva, Olesya
Slade, Kimberly Sue
Thomas, Anita
Tsaur, Igor
Cinatl, Jindrich
Michaelis, Martin
Efferth, Thomas
Haferkamp, Axel
Juengel, Eva
Titel: Shikonin reduces growth of docetaxel-resistant prostate cancer cells mainly through necroptosis
Online-Publikationsdatum: 31-Mai-2021
Sprache des Dokuments: Englisch
Zusammenfassung/Abstract: The prognosis for advanced prostate carcinoma (PCa) remains poor due to development of therapy resistance, and new treatment options are needed. Shikonin (SHI) from Traditional Chinese Medicine has induced antitumor effects in diverse tumor entities, but data related to PCa are scarce. Therefore, the parental (=sensitive) and docetaxel (DX)-resistant PCa cell lines, PC3, DU145, LNCaP, and 22Rv1 were exposed to SHI [0.1–1.5 μM], and tumor cell growth, proliferation, cell cycling, cell death (apoptosis, necrosis, and necroptosis), and metabolic activity were evaluated. Correspondingly, the expression of regulating proteins was assessed. Exposure to SHI time- and dose-dependently inhibited tumor cell growth and proliferation in parental and DX-resistant PCa cells, accompanied by cell cycle arrest in the G2/M or S phase and modulation of cell cycle regulating proteins. SHI induced apoptosis and more dominantly necroptosis in both parental and DX-resistant PCa cells. This was shown by enhanced pRIP1 and pRIP3 expression and returned growth if applying the necroptosis inhibitor necrostatin-1. No SHI-induced alteration in metabolic activity of the PCa cells was detected. The significant antitumor effects induced by SHI to parental and DX-resistant PCa cells make the addition of SHI to standard therapy a promising treatment strategy for patients with advanced PCa.
DDC-Sachgruppe: 610 Medizin
610 Medical sciences
Veröffentlichende Institution: Johannes Gutenberg-Universität Mainz
Organisationseinheit: FB 04 Medizin
Veröffentlichungsort: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-5928
Version: Published version
Publikationstyp: Zeitschriftenaufsatz
Weitere Angaben zur Dokumentart: Scientific article
Nutzungsrechte: CC BY
Informationen zu den Nutzungsrechten: https://creativecommons.org/licenses/by/4.0/
Zeitschrift: Cancers
13
4
Seitenzahl oder Artikelnummer: 882
Verlag: MDPI
Verlagsort: Basel
Erscheinungsdatum: 2021
ISSN: 2072-6694
URL der Originalveröffentlichung: https://doi.org/10.3390/cancers13040882
DOI der Originalveröffentlichung: 10.3390/cancers13040882
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