Eupatilin Inhibits the Proliferation and Migration of Prostate Cancer Cells through Modulation of PTEN and NF-ΚB Signaling

Background: Despite advances in the treatment of prostate cancer, side effects and the risks of developing drug resistance require new therapeutic agents. Eupatilin is a secondary metabolite of Artemisia asiatica and has shown potential anti-tumor activity in some cancers, but its potential in prostate cancer treatment has not yet been evaluated. Objective: The aim of the study was to investigate the effectiveness of eupatilin on prostate cancer cell proliferation and migration. Methods: Human prostate cancer PC3 and LNCaP cells were exposed to eupatilin and its efficacy on cell survival was determined by the MTT test. Apoptosis and cell cycle phases were evaluated by an image-based cytometer. Cell migration and invasion were evaluated by wound healing and matrigel migration assays; the expression of mRNA and protein was assessed by RT-qPCR and Western blot, respectively. Results: Eupatilin time- and dose-dependently reduced the viability of prostate cancer cells. Exposure of PC3 cells to 12.5μM-50μM eupatilin resulted in apoptosis by upregulating the expression of caspase 3, Bax and cytochrome c. Annexin V assessment also confirmed that eupatilin causes apoptosis. The treatment significantly upregulated the mRNA expression of p53, p21, and p27, causing cell cycle arrest in the G1 phase. Administration of eupatilin inhibited migration and invasion of the cells by downregulating the expression of Twist, Slug and MMP-2, -7. In addition, the agent increased protein expression of tumor suppressor PTEN, while transcription factor NF-ΚB expression was reduced. Conclusion: Eupatilin strongly prevents the proliferation of prostate cancer cells, and suppresses migration and invasion. Due to its therapeutic potential, the clinical use of eupatilin in prostate cancer should also be supported by in vivo studies.