Abstract
Pancreatic cancer (PC) is the fourth leading cause of all cancer-related deaths. Despite major improvements in treating PC, low survival rate remains a major challenge, indicating the need for alternative approaches, including herbal medicine. Among medicinal plants is Ziziphus nummularia (family Rhamnaceae), which is a thorny shrub rich in bioactive molecules. Leaves of Ziziphus nummularia have been used to treat many pathological conditions, including cancer. However, their effects on human PC are still unknown. Here, we show that the treatment of human pancreatic ductal adenocarcinoma cells (Capan-2) with Ziziphus nummularia ethanolic extract (ZNE) (100–300 μg/mL) attenuated cell proliferation in a time- and concentration-dependent manner. Pretreatment with N-acetylcysteine, an ROS scavenger, attenuated the anti-proliferative effect of ZNE. In addition, ZNE significantly decreased the migratory and invasive capacity of Capan-2 with a concomitant downregulation of integrin α2 and increased cell–cell aggregation. In addition, ZNE inhibited in ovo angiogenesis as well as reduced VEGF and nitric oxide levels. Furthermore, ZNE downregulated the ERK1/2 and NF-κB signaling pathways, which are known to drive tumorigenic and metastatic events. Taken together, our results suggest that ZNE can attenuate the malignant phenotype of Capan-2 by inhibiting hallmarks of PC. Our data also provide evidence for the potential anticancer effect of Ziziphus nummularia, which may represent a new resource of novel anticancer compounds, especially ones that can be utilized for the management of PC.
Highlights
Cancer is the second leading cause of death worldwide, accounting for 13% of global mortalities [1]
A chemical extracted from Z. nummularia decreased the tumor volume of Ehrlich ascites carcinoma-bearing mice, and more importantly, it increased their survival [13]. These studies suggest that Z. nummularia may have a beneficial effect in the fight against cancer, which prompted us to test the effect of this shrub on Pancreatic cancer (PC), which is a rather formidable and unpreventable type of cancer [15]
We examined the effect of the Z. nummularia ethanolic extract (ZNE) on the malignant phenotype of human pancreatic ductal adenocarcinoma cells (Capan-2)
Summary
Cancer is the second leading cause of death worldwide, accounting for 13% of global mortalities [1]. Commonly known as Sidr, is a branched thorny shrub belonging to the family Rhamnaceae [8] It grows largely in arid and dry areas [9], and it has been used in folk medicine [10,11]. A chemical extracted from Z. nummularia decreased the tumor volume of Ehrlich ascites carcinoma-bearing mice, and more importantly, it increased their survival [13]. These studies suggest that Z. nummularia may have a beneficial effect in the fight against cancer, which prompted us to test the effect of this shrub on PC, which is a rather formidable and unpreventable type of cancer [15]. The roles of ROS and NF-κB in the ZNE-modulated proliferation of Capan-2 cells were tested
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