Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-5928
Authors: | 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 |
Title: | Shikonin reduces growth of docetaxel-resistant prostate cancer cells mainly through necroptosis |
Online publication date: | 31-May-2021 |
Year of first publication: | 2021 |
Language: | english |
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: | 610 Medizin 610 Medical sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 04 Medizin |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-5928 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
Document type specification: | Scientific article |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Cancers 13 4 |
Pages or article number: | 882 |
Publisher: | MDPI |
Publisher place: | Basel |
Issue date: | 2021 |
ISSN: | 2072-6694 |
Publisher URL: | https://doi.org/10.3390/cancers13040882 |
Publisher DOI: | 10.3390/cancers13040882 |
Appears in collections: | JGU-Publikationen |
Files in This Item:
File | Description | Size | Format | ||
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markowitsch_sascha_d.-shikonin_reduc-20210514144150228.pdf | 7.16 MB | Adobe PDF | View/Open |