Abstract
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.
Highlights
Prostate carcinoma (PCa) is the most common cancer in men without curative therapy for metastatic disease, diverse therapeutic strategies have contributed to prolonged survival and reduced therapy-induced complications [1,2,3]
Tumor cell growth and proliferation of parental and DX-resistant prostate cancer (PCa) cells as well as of ‘normal/non-tumor’ cells were evaluated after ART application
Besides the growth inhibitory effect in parental PCa cells, the current study revealed that ART induces anti-growth and antiproliferative activity in DX-resistant DU145, PC3, and LNCaP cells
Summary
Prostate carcinoma (PCa) is the most common cancer in men without curative therapy for metastatic disease, diverse therapeutic strategies have contributed to prolonged survival and reduced therapy-induced complications [1,2,3]. Due to existing and emerging resistance to DX, innovative therapeutic approaches are essential in bringing new effective treatment options to patients with castration- and chemotherapy-resistant PCa. In the past decades, the demand for complementary and alternative medicine (CAM) has increased and is reflected by its use among cancer patients, ranging from 30 - 90%, depending on the country, culture, cancer type and stage [9,10,11]. Combination therapy with natural compounds requires thorough investigation to increase efficacy while minimizing side effects. Since valid scientific investigation regarding the anti-tumor activity of natural compounds is frequently lacking, contraindications to their use cannot be ruled out [12, 13]
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