JOURNEY OF THE SAPONIN FROM THE PLANT TO THE FORMULATION FOR BLOCKING TUMOR ACTIVITIES

Year 2023, Volume: 27 Issue: Current Research Topıcs In Pharmacy: Drug Delivery, 17 - 19, 28.06.2025

Burcu Üner , Ahmet Doğan Ergin , Ayça Altay Benetti Juste Baranauskaıte Ortasöz

Abstract

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

References

• [1] Ockenga J, Vogel A, Teich N, Keim V, Manns MP, Strassburg CP. UDP glucuronosyltransferase (UGT1A7) gene polymorphisms increase the risk of chronic pancreatitis and pancreatic cancer. Gastroenterology 2003; 124: 1802-1808 [CrossRef].
• [2] Otte JM, Kiehne K, Schmitz F, Fölsch UR, Herzig KH. C-met protooncogene expression and its regulation by cytokines in the regenerating pancreas and pancreatic cancer cells. Scand J Gastroenterol. 2000; 35: 90-95 [CrossRef].
• [3] Xu XH, Li T, Fong CM, Chen X, Chen XJ, Wang YT, Huang MQ, Lu JJ. Saponins from Chinese medicines as anticancer agents. Molecules. 2016;21(10):1326 [CrossRef].
• [4] Celep AGS, Yilmaz S, Coruh N. Antioxidant capacity and cytotoxicity of Aesculus hippocastanum on breast cancer MCF-7 cells. J Food Drug Anal. 2012; 20 (3): 17 [CrossRef].
• [5] Boateng-Marfo Y, Dong Y, Ng WK, Lin H-S. Artemether-loaded zein nanoparticles: An innovative intravenous dosage form for the management of severe malaria. Int J Mol Sci. 2021; 22(3):1141 [CrossRef].