Comparative Investigation of the Cytotoxic Effects of Carnosic Acid and Gallic Acid on the HNF1A Gene in PANC-1 Pancreatic Cells

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Gacar G., Ünal E. D., Yusufoğlu S.

Acıbadem Üniversitesi Sağlık Bilimleri Dergisi, ss.1-12, 2026 (TRDizin)

Özet

ABSTRACT Objective: Pancreatic cancer is one of the most aggressive malignancies and is associated with a high mortality rate due to late diagnosis and limited therapeutic options. Natural phenolic compounds have attracted considerable attention because of their potential anticancer activities. This study aimed to comparatively investigate the cytotoxic and apoptotic effects of gallic acid (GA) and carnosic acid (CA) on HNF1A gene expression in PANC-1 pancreatic cancer cells, and to evaluate their combined effects in the presence of mesenchymal stem cells (MSCs). Methods: Different experimental groups consisting of PANC-1 cells, MSCs, GA, and CA were established using an indirect co-culture model. Cell viability was evaluated using the WST-1 assay, while apoptosis levels were determined by Annexin V-PI flow cytometry analysis. Changes in HNF1A gene expression were analyzed using quantitative real-time PCR (qPCR). Results: The results demonstrated that treatment with GA and CA significantly reduced the viability of PANC-1 cells and increased apoptotic cell populations. The combined treatment of GA (50 µM) and CA (25 µM) in the presence of MSCs showed the most pronounced inhibitory effect on cancer cell proliferation. Furthermore, gene expression analysis revealed that this combination significantly downregulated HNF1A expression, suggesting a potential regulatory effect on pancreatic cancer progression. Conclusion: The findings indicate that gallic acid and carnosic acid exert antiproliferative and pro-apoptotic effects on PANC-1 pancreatic cancer cells, particularly in combination with MSCs. The observed decrease in HNF1A gene expression suggests that these compounds may contribute to the modulation of molecular mechanisms involved in pancreatic tumor progression. These results highlight the potential of GA and CA as promising candidates for the development of novel therapeutic strategies for pancreatic cancer. Keywords: Carnosic acid, Gallic acid, HNF1A, Mesenchymal stem cells, Pancreatic cancer