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

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, th...

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Published in:Cancers 2021-02, Vol.13 (4), p.882
Main Authors: Markowitsch, Sascha D, Juetter, Kira M, Schupp, Patricia, Hauschulte, Kristine, Vakhrusheva, Olesya, Slade, Kimberly Sue, Thomas, Anita, Tsaur, Igor, Cinatl, Jr, Jindrich, Michaelis, Martin, Efferth, Thomas, Haferkamp, Axel, Juengel, Eva
Format: Article
Language:English
Subjects:
Antitumor activity
Apoptosis
Bladder cancer
Cancer therapies
Cell cycle
Cell death
Cell growth
Cell proliferation
Cyclin-dependent kinases
Drug dosages
Gastric cancer
Kinases
Metastasis
Necroptosis
Pancreatic cancer
Prostate
Prostate cancer
Prostate carcinoma
Proteins
S phase
Shikonin
Traditional Chinese medicine
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13040882