Abstract
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) was one of the most aggressive and deadly cancers, with limited treatment options and unfavorable prognosis. Tormentic acid, a pentacyclic triterpene, has shown promising anticancer properties in various cancers. However, its effects on PDAC remain unclear. The aim of this study was to assess the anticancer property of tormentic acid in PDAC cell lines and to attempt to understand its mechanism of action. METHODS: Effects of tormentic acid were tested in PDAC cell lines (PANC-1 and MIA PaCa-2) by employing several assays such as Cell Counting Kit-8 (CCK-8) assay for cell viability, comet assay for DNA damage, Annexin V/PI staining for apoptosis, flow cytometry for cell cycle analysis and wound healing assays for cell migration. Gene expression analysis was conducted to determine changes in critical apoptotic and cell cycle controlling proteins. RESULTS: Tormentic acid significantly reduced the viability of PDAC cells in a dose-dependent manner. It induced DNA damage, as evidenced by comet tail formation, and promoted apoptosis through the activation of caspases-3 and -9, and modulation of Bax and Bcl-2 expression. Tormentic acid also caused a G1 cell cycle arrest, with upregulation of p21 and downregulation of cyclins D and E. Furthermore, tormentic acid inhibited PDAC cell migration by downregulating matrix metalloproteinases (MMPs). CONCLUSIONS: Tormentic acid showed potent anticancer effects in PDAC cells by inducing apoptosis, arresting the cell cycle, and suppressing metastasis. These findings highlight its potential as a therapeutic agent for PDAC treatment.