en بیولوژی سلولی- مولکولی Cellular and Molecular Biology پژوهشي Original Research <div style="text-align: justify;"><strong>Background</strong>: Ovarian cancer is one of the most lethal gynecologic cancers in the world. It has also characterized by late diagnosis, high recurrence rate, and poor &nbsp;prognosis. The advanced stage at diagnosis and the development of chemoresistance are major challenges in its treatment, leading to limited therapeutic options and decreased survival rates. Natural products have emerged as a promising source of novel anticancer agents due to their diverse bioactive compounds and potential to target multiple signaling pathways involved in cancer initiation and progression.<br> <strong>Objectives</strong>: Ovarian cancer metastasis is the leading cause of cancer-related deaths in women worldwide. The effects of Quillaja saponaria bark saponin (QBS) on the viability and epithelial-mesenchymal transition (EMT) potential of human ovarian epithelial SKOV-3 and A2780 cells, and the cytotoxicity effect of QBS in the rat ovarian cancer model have been investigated.<br> <strong>Methods</strong>: The cytotoxicity of QBS against SKOV3 and A2780 cells was evaluated using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to calculate IC50 values. The scratch assay assessed cell migration. To explore molecular changes in metastasis, the expression of key EMT-related genes, including ITGA5, MMP2, Zeb1, and CDH1 was measured by real-time polymerase chain reaction. For the in vivo assay, the 7,12-dimethylbenz[a]anthracene (DMBA)-induced ovarian cancer rat model was used.&nbsp;<br> <strong>Results</strong>: The MTT assay demonstrated that QBS did not exert significant toxicity on NIH3T3 as normal cells; nevertheless, it induced cytotoxicity against A2780 and SKOV3 cells in a dose and time-dependent manner; IC50 was determined as 82 and 77 &mu;g/mL for SKOV3 and A2780 cells, respectively. The scratch assay revealed that QBS significantly attenuated cell invasion at sub-IC50 concentrations (20 and 30 &micro;g/mL). Gene expression indicated down-regulation of Zeb1, ITGA5, and MMP2 at the IC50 value of both SKOV3 and A2780 cells (P&le;0.001). Also, up-regulation of CDH1 in A2780 cells at the IC50 value was significant (P&le;0.001). The in vivo assay showed that QBS significantly reduced tumor growth (P&le;0.01) and protected rats against 7,12- DMBA-induced ovarian cancer, with optimal effect of 16 mg/kg.<br> <strong>Conclusion</strong>: Overall, QBS can offer a potent cytotoxic agent against ovarian cancer cells in vitro and in vivo. However, this hypothesis requires further investigation to discover the molecular signaling pathway in human ovarian cancer cells.</div> Ovarian cancer, Migration, Quillaja saponaria bark saponin (QBS), ITGA5, MMP2, Zeb1, CDH1 195 206 http://pbr.mazums.ac.ir/browse.php?a_code=A-10-1469-2&slc_lang=en&sid=1 Raoufeh Koochaki Raoufeh.koochaki73@gmail.com 0000-0003-3384-0316 No Department of Cell & Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran. Mohammad Nabiuni nabiuni@khu.ac.ir 0000-0002-0349-6676 Yes Department of Cell & Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran. Elaheh Amini elaheh.amini@khu.ac.ir 0000-0002-0951-4572 No Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.