Comparative In Vitro Cytotoxicity of Piper betle Leaf Extracts in KRAS G12D-Mutant Pancreatic Cancer Cell Lines

Vollständiger Abstract

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Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers worldwide, with limited treatment options and a high prevalence of oncogenic KRAS mutations. Piper betle contains numerous bioactive phytochemicals with reported anticancer activities, although its activity against pancreatic cancer remains incompletely characterized. This study evaluated the phytochemical composition of P. betle leaf extracts and the cell viability effects of ethanolic extracts against human KRAS G12D-mutant pancreatic cancer cell lines (PANC-1, AsPC-1, Panc 02.03, Panc 04.03, Panc 08.13 and Panc 10.05). Phytochemical screening, total phenolic content (TPC), total flavonoid content (TFC) and gas chromatography–mass spectrometry (GC-MS) analyses were performed to characterize the extracts. The ethanolic extracts exhibited higher extraction yield (17.26%), TPC (395.94 ± 0.010 mg GAE/g) and TFC (121.28 ± 0.009 mg QE/g) than aqueous extracts. GC-MS analysis tentatively identified phenylpropanoid compounds, including chavicol, chavibetol, and eugenol. Based on these findings, the ethanolic extract was selected for biological evaluation. Treatment significantly reduced cell viability in a concentration-dependent manner across all pancreatic cancer cell lines, with estimated IC50 values ranging from 21.54 to 54.91 µg/mL. These findings suggest that ethanolic P. betle leaf extract possesses promising biological activity and support further studies to identify its active constituents and elucidate their mechanisms of action.