DataSheet_1_Artesunate Inhibits the Growth Behavior of Docetaxel-Resistant Prostate Cancer Cells.pdf

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.

针对晚期转移性前列腺癌（PCa），迫切需要探索新的治疗策略。传统中医药中使用的植物化学成分似乎具有肿瘤抑制特性。因此，本研究旨在探究青蒿素（ART）对治疗敏感型（亲本）及多西他赛（DX）耐药型PCa细胞的生长抑制作用。本研究对亲本和DX耐药型PCa细胞系DU145、PC3和LNCaP进行了青蒿素（ART）[1-100 µM]的处理。未经ART处理的细胞及‘非癌性’细胞作为对照组。评估了细胞生长、增殖、细胞周期进程、细胞死亡以及相关蛋白的表达。结果显示，ART在剂量和时间依赖性上显著限制了亲本和DX耐药型PCa细胞的生长和增殖，而对‘正常，非癌性’细胞则无显著影响。ART诱导的生长和增殖抑制伴随G0/G1期阻滞及细胞周期激活蛋白的下调，这在所有DX耐药型PCa细胞和亲本LNCaP细胞中均可见。在亲本和DX耐药型PC3和LNCaP细胞系中，ART还促进了细胞凋亡。在亲本和DX耐药型DU145细胞中，ART通过增加活性氧（ROS）诱导铁死亡。ART在三种PCa细胞系中均表现出抗癌活性，但其作用机制各不相同。因此，在晚期前列腺癌的治疗中，ART有望作为传统疗法的辅助治疗手段。