Urtica dioica leaf infusion enhances cisplatin-induced apoptosis in ovarian cancer cells in vitro.

Abstract

Urtica Dioica (UD) or stinging nettle has been widely used for its therapeutic benefits and biological activities. Recent studies have reported its beneficial effect in treating cancer, most importantly when combined with chemotherapeutic drugs. To our knowledge, no studies investigated the potential effect of UD to enhance the sensitivity of ovarian cancer cells to cisplatin. In this study we aim to investigate whether this combination might possess anti-proliferative, pro-apoptotic, and anti-metastatic properties on one of the most aggressive ovarian cancer cell lines, SKOV-3 cells, in vitro. To elucidate its therapeutic values, cytotoxicity and DNA fragmentation assays were performed along with cell cycle and apoptosis assays using flow cytometry, RT-qPCR, and western blot analysis. Additionally, wound healing and trans-well migration assays were used to study the effect of this combination on the motility of ovarian cancer cells. Results showed that the combination of nettle extract and cisplatin significantly decreased the proliferation of SKOV-3 cells in a dose and time-dependent manner compared to each treatment alone by inducing cellular death as revealed by major apoptotic markers including phosphatidylserine translocation to the outer membrane leaflet, DNA fragmentation, and the upregulation of cleaved PARP protein. Further evaluation verified the activation of extrinsic apoptosis via the caspase-dependent pathway as demonstrated by the upregulated expression levels of caspases 3 and 8. Finally, the combination of nettle tea and cisplatin showed an inhibitory effect on the motility and migratory capacities of SKOV-3 cells. As a result, Urtica Dioica leaf infusion was found effective in enhancing cisplatin-induced apoptosis while inhibiting the tumor progression of one of the most aggressive ovarian cancer cells in vitro.