Vakhrusheva Olesya, Erb Holger H H, Bräunig Vitus, Markowitsch Sascha D, Schupp Patricia, Baer Patrick C, Slade Kimberly Sue, Thomas Anita, Tsaur Igor, Puhr Martin, Culig Zoran, Cinatl Jindrich, Michaelis Martin, Efferth Thomas, Haferkamp Axel, Juengel Eva
Department of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, Germany.
Department of Urology, University of Dresden, Dresden, Germany.
Front Oncol. 2022 Feb 7;12:789284. doi: 10.3389/fonc.2022.789284. eCollection 2022.
Novel therapeutic strategies are urgently needed for advanced metastatic prostate cancer (PCa). Phytochemicals used in Traditional Chinese Medicine seem to exhibit tumor suppressive properties. Therefore, the therapeutic potential of artesunate (ART) on the progressive growth of therapy-sensitive (parental) and docetaxel (DX)-resistant PCa cells was investigated. Parental and DX-resistant PCa cell lines DU145, PC3, and LNCaP were incubated with artesunate (ART) [1-100 µM]. ART-untreated and 'non-cancerous' cells served as controls. Cell growth, proliferation, cell cycle progression, cell death and the expression of involved proteins were evaluated. ART, dose- and time-dependently, significantly restricted cell growth and proliferation of parental and DX-resistant PCa cells, but not of 'normal, non-cancerous' cells. ART-induced growth and proliferation inhibition was accompanied by G0/G1 phase arrest and down-regulation of cell cycle activating proteins in all DX-resistant PCa cells and parental LNCaP. In the parental and DX-resistant PC3 and LNCaP cell lines, ART also promoted apoptotic cell death. Ferroptosis was exclusively induced by ART in parental and DX-resistant DU145 cells by increasing reactive oxygen species (ROS). The anti-cancer activity displayed by ART took effect in all three PCa cell lines, but through different mechanisms of action. Thus, in advanced PCa, ART may hold promise as a complementary treatment together with conventional therapy.
晚期转移性前列腺癌（PCa）迫切需要新的治疗策略。中药中使用的植物化学物质似乎具有肿瘤抑制特性。因此，研究了青蒿琥酯（ART）对治疗敏感（亲本）和多西他赛（DX）耐药的PCa细胞进行性生长的治疗潜力。将亲本和DX耐药的PCa细胞系DU145、PC3和LNCaP与青蒿琥酯（ART）[1-100µM]一起孵育。未用ART处理的细胞和“非癌”细胞作为对照。评估细胞生长、增殖、细胞周期进程、细胞死亡以及相关蛋白的表达。ART剂量和时间依赖性地显著限制了亲本和DX耐药PCa细胞的生长和增殖，但对“正常、非癌”细胞没有影响。ART诱导的生长和增殖抑制伴随着所有DX耐药PCa细胞和亲本LNCaP中G0/G1期阻滞和细胞周期激活蛋白的下调。在亲本和DX耐药的PC3和LNCaP细胞系中，ART还促进了凋亡性细胞死亡。在亲本和DX耐药的DU145细胞中，ART通过增加活性氧（ROS）专门诱导铁死亡。ART显示的抗癌活性在所有三种PCa细胞系中均有作用，但作用机制不同。因此，在晚期PCa中，ART作为与传统疗法联合的辅助治疗可能具有前景。
