Stevia Leaf Extract Fermented with Plant-Derived SN13T Displays Anticancer Activity to Pancreatic Cancer PANC-1 Cell Line.

Pancreatic cancer is a highly malignant tumor that remains a significant global health burden. In this study, we demonstrated the anticancer potential of stevia leaf extract fermented with plant-derived (.) SN13T strain. Evaluation of antioxidant capacity (including DPPH and ABTS radical scavenging activities and HO-induced oxidative damage repair in HEK-293 cells), as well as cytotoxicity against pancreatic cancer cells (PANC-1) and non-cancerous human embryonic kidney (HEK-293), revealed that the fermented extract exhibited significantly enhanced antioxidant activity and cytotoxicity against PANC-1 cells while showing minimal toxicity to HEK-293 cells compared to the unfermented extract. Further, validation through clonogenic, migration, and wound-healing assays demonstrated that the fermented extract effectively inhibited the proliferation and migration of PANC-1 cells. The active compound in the fermented extract has been identified as chlorogenic acid methyl ester (CAME), with a concentration of 374.4 μg/mL. Flow cytometry analysis indicated that CAME significantly arrested PANC-1 cells in the G/G phase and induced apoptosis. Furthermore, CAME upregulated the expression of pro-apoptotic genes , , /, , and , while downregulating the anti-apoptotic gene . These findings suggest that CAME exerts potent cytotoxic effects on PANC-1 cells by inhibiting cell proliferation and migration, arresting the cell cycle, and regulating apoptosis-related gene expression. In conclusion, stevia leaf extract fermented with SN13T, which contains CAME, may serve as a promising candidate for pancreatic cancer treatment.