Ziziphus nummularia Attenuates the Malignant Phenotype of Human Pancreatic Cancer Cells: Role of ROS

Molecules

Hadi M. Yassine¹  Ali H. Eid²  Adnan Badran³  Yusra Al Dhaheri⁴  Rabah Iratni⁴  Elias Baydoun⁵  Manal M. Fardoun⁵  Joelle Mesmar⁵  Rola Abdallah⁵ 

[1] Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar;Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar;Department of Basic Sciences, University of Petra, Amman P.O. Box 961343, Jordan;Department of Biology, College of Science, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab Emirates;Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut P.O. Box 11-0236, Lebanon;

关键词: herbal medicine;    pancreatic cancer;    malignant phenotype;    ROS;    Ziziphus nummularia;   

DOI  :  10.3390/molecules26144295

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown