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

Cancers

Patricia Schupp¹  Eva Juengel¹  Anita Thomas¹  Axel Haferkamp¹  Olesya Vakhrusheva¹  Igor Tsaur¹  Sascha D. Markowitsch¹  Kira M. Juetter¹  Kristine Hauschulte¹  Kimberly Sue Slade¹  Martin Michaelis²  Jindrich Cinatl³  Thomas Efferth⁴ 

[1] Department of Urology and Pediatric Urology of the University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany;Industrial Biotechnology Centre and School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK;Institute of Medical Virology, Goethe-University, 60596 Frankfurt, Germany;Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudingerweg 5, 55128 Mainz, Germany;

关键词: prostate cancer (PCa);    docetaxel (DX) resistance;    shikonin (SHI);    Traditional Chinese Medicine (TCM);    growth inhibition;    apoptosis;   

DOI  :  10.3390/cancers13040882

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown