Cell Toxicity of Kadsuric Acid from Kadsura coccinea in Human Pancreatic Cancer Cells Through Caspase/PARP Pathway: In Vitro and In Silico Approach

• Published in: Revista brasileira de farmacognosia Vol. 34; no. 6; pp. 1401 - 1412
• Main Authors: Nguyen, Tan Khanh, Tran, Manh Hung, Trung, Truong Tan, Pham, Long-Hung Dinh, Truong, Phu Chi Hieu, Pham, Phu Tran Vinh
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2024
• Subjects: Medicine; Original Article; Pharmacy; Repairing DNA damage; Poly ADP-ribose polymerase; Schisandraceae; Anticancer; Apoptosis
• ISSN: 1981-528X; 1981-528X
• DOI: 10.1007/s43450-024-00588-7

Kadsuric acid, a major triterpenoid isolated from the leaves of Vietnamese Kadsura coccinea (Lem.) A.C.Sm., Schisandraceae, exhibited potent cytotoxic effects in some human cancer cells. In this study, the effects of kadsuric acid on pancreatic cancer cells PANC-1 were investigated. The results showed that kadsuric acid exhibited dose-dependent cytotoxicity against PANC-1 with an IC 50 value of 14.5 ± 0.8 µM. Kadsuric acid effectively activated caspase-3 by increasing the level of enzyme cleavage by 1–2 times after 12 and 24 h, and by more than 3–4 times compared to the negative control. In addition, this compound enhanced both two types of cysteine-aspartic acid proteases, including caspase-3 and caspase-9 through protein expressions. Western blot analysis also indicated that kadsuric acid reduced poly [ADP-ribose] polymerase 1 (PARP1) expression in PANC-1 cells. For underlying mechanism insights, molecular modeling methods were applied to investigate the binding interaction between kadsuric acid and PARP1. Compared to the co-crystallized ligand, kadsuric acid displayed a stronger binding affinity (− 9.3 kcal/mol). A molecular dynamics simulation showed that the complex is stable over 200 ns. Taken together, it can be determined that kadsuric acid can interact with the DNA of human pancreatic cancer cells through the intrinsic caspase/PARP1 pathway. This study can guide future research on kadsuric acid as a PARP1 inhibitor for cancer treatment. Graphical Abstract