Nafeh Perla, Nafeh Guy, Younes Maria, Chaaban Ahlam, El Bitar Louna, Ibrahim José-Noel, Kobeissy Philippe H, Rizk Sandra
Department of Biological Sciences, Lebanese American University, P.O. Box 36, Byblos, Lebanon.
Department of Biological Sciences, Lebanese American University, Beirut, 1102-2801, Lebanon.
BMC Complement Med Ther. 2025 Aug 13;25(1):304. doi: 10.1186/s12906-025-05053-z.
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.
荨麻（UD）或刺荨麻因其治疗功效和生物活性而被广泛使用。最近的研究报道了其在治疗癌症方面的有益作用，最重要的是与化疗药物联合使用时。据我们所知，尚无研究调查荨麻对增强卵巢癌细胞对顺铂敏感性的潜在影响。在本研究中，我们旨在调查这种联合用药在体外对最具侵袭性的卵巢癌细胞系之一SKOV-3细胞是否具有抗增殖、促凋亡和抗转移特性。为了阐明其治疗价值，进行了细胞毒性和DNA片段化检测，同时使用流式细胞术、RT-qPCR和蛋白质印迹分析进行细胞周期和凋亡检测。此外，还使用伤口愈合和Transwell迁移检测来研究这种联合用药对卵巢癌细胞运动性的影响。结果表明，与单独的每种治疗相比，荨麻提取物和顺铂的联合用药通过诱导细胞死亡，以剂量和时间依赖性方式显著降低了SKOV-3细胞的增殖，主要凋亡标志物包括磷脂酰丝氨酸转运至外膜小叶、DNA片段化以及裂解的PARP蛋白上调均揭示了这一点。进一步评估证实了通过半胱天冬酶依赖性途径激活外源性凋亡，半胱天冬酶3和8的表达水平上调证明了这一点。最后，荨麻茶和顺铂的联合用药对SKOV-3细胞的运动性和迁移能力具有抑制作用。因此，发现荨麻叶浸剂在体外可有效增强顺铂诱导的凋亡，同时抑制最具侵袭性的卵巢癌细胞之一的肿瘤进展。
