TY - JOUR
T1 - Ziziphus nummularia attenuates the malignant phenotype of human pancreatic cancer cells
T2 - Role of ros
AU - Mesmar, Joelle
AU - Fardoun, Manal M.
AU - Abdallah, Rola
AU - Al Dhaheri, Yusra
AU - Yassine, Hadi M.
AU - Iratni, Rabah
AU - Badran, Adnan
AU - Eid, Ali H.
AU - Baydoun, Elias
N1 - Funding Information:
This work was supported by the American University of Beirut (Grant # MPP 320133 to A.E.), University of Petra Grant to A.B., E.B. and A.E., URB grant of American University of Beirut (to E.B.), and UAEU Program for Advanced Research, grant number 31S398-UPAR (Y.A.).
Funding Information:
Funding: This work was supported by the American University of Beirut (Grant # MPP 320133 to A.E.), University of Petra Grant to A.B., E.B. and A.E., URB grant of American University of Beirut (to E.B.), and UAEU Program for Advanced Research, grant number 31S398-UPAR (Y.A.).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/7/2
Y1 - 2021/7/2
N2 - 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 nummu-laria (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.
AB - 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 nummu-laria (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.
KW - Herbal medicine
KW - Malignant phenotype
KW - Pancreatic cancer
KW - ROS
KW - Ziziphus nummularia
UR - http://www.scopus.com/inward/record.url?scp=85111101682&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111101682&partnerID=8YFLogxK
U2 - 10.3390/molecules26144295
DO - 10.3390/molecules26144295
M3 - Article
C2 - 34299570
AN - SCOPUS:85111101682
SN - 1420-3049
VL - 26
JO - Molecules
JF - Molecules
IS - 14
M1 - 4295
ER -