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Shikonin Reduces Growth of Docetaxel-Resistant Prostate Cancer Cells Mainly through Necroptosis

Markowitsch, Sascha D., Juetter, Kira M., Schupp, Patricia, Hauschulte, Kristine, Vakhrusheva, Olesya, Slade, Kimberly Sue, Thomas, Anita, Tsaur, Igor, Cinatl, Jindrich, Michaelis, Martin, and others. (2021) Shikonin Reduces Growth of Docetaxel-Resistant Prostate Cancer Cells Mainly through Necroptosis. Cancers, 13 (4). p. 882. ISSN 2072-6694. (doi:10.3390/cancers13040882) (KAR id:87535)

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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.

Item Type: Article
DOI/Identification number: 10.3390/cancers13040882
Uncontrolled keywords: prostate cancer (PCa); docetaxel (DX) resistance; shikonin (SHI); Traditional Chinese Medicine (TCM); growth inhibition; apoptosis; necroptosis
Subjects: R Medicine > RC Internal medicine > RC254 Neoplasms. Tumors. Oncology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Martin Michaelis
Date Deposited: 10 Apr 2021 08:18 UTC
Last Modified: 12 Apr 2021 08:50 UTC
Resource URI: (The current URI for this page, for reference purposes)
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