2Department of Pharmaceutical Technology, Faculty of Pharmacy, Trakya University, Edirne, Turkey
3Department of Neuroscience, University of Turin, Turin, Italy
4Faculty of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore
5Department of Pharmaceutical Technology, Faculty of Pharmacy, Yeditepe University, Istanbul, Turkey DOI : 10.29228/jrp.505 Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and incurable malignancy that is anticipated to be the second leading cause of cancer-related death by 2030. Several signaling pathways involved in growth and proliferation are activated in PDAC. Notwithstanding the progress in pancreatic cancer research over the past decade, effective treatment regimens are lacking. Chemotherapy and radiation therapy are often ineffective [1, 2]. Saponin-derived compounds have proven to be promising in treating many types of cancer, and it is anticipated that they can be used as drugs [3,4]. In this study, mycelial formulations were created based on a DoE perspective with triterpenoid saponins obtained from the marketed product (ABX-Abraxane)[5]. Aesculus hippocastanum L. has used to get saponin. Following characterization studies of micelles (FT-IR, DLS, and TEM), cell-binding and Papp values were analyzed using the human pancreas adenocarcinoma ascites metastasis cell line (AsPC-1).
In addition, the levels of proto-oncogenes (KRAS, CTNNB1 (β-catenin), PIK3CA, and AKT) involved in pancreatic carcinogenesis were measured by using ELISA, and the mitochondrial membrane permeability and alterations of oxidative stress levels have been measured by flow cytometry. As a result of the treatment with the control group and micelle formulations on AsPC-1 cells, Annexin-V positive stained areas showed a positive result in PI (late apoptotic). When the apoptotic effect on AsPC-1 cells as a result of the application of micelle formulation was evaluated in flow cytometry at the end of 12 (AsPC-1 72.3% to 47.2%) and 24 (AsPC-1 47.2% to 16.3%) hour treatments, a decrease in cell viability percentage was observed, while an increase in the percentage of necrotic cells was determined. Besides, it was determined that there was a significant increase in ROS levels with micelle formulation compared to the control (13.5 to 67.8).
Keywords : Pancreatic ductal adenocarcinoma, micelle, saponins, AsPC-1