Garcinol sensitizes human pancreatic adenocarcinoma cells to gemcitabine in association with micro RNA signatures

Background Alterations in micro RNA (mi RNA /mi R ) genes are of biological importance in the pathophysiology of cancers, including pancreatic cancer ( P a C a). Although growing evidence supports the role of mi RNA in cancer, their response to dietary phytochemicals is less known. Previously, we showed that garcinol induces P a C a cell growth arrest and apoptosis in vitro. The present study, discusses chemo‐sensitization by garcinol in synergism with first‐line P a C a drug, gemcitabine. The mi RNA expression profile of gemcitabine‐resistant P anc‐1 cells treated with garcinol and/or gemcitabine was also evaluated. Methods and results Garcinol synergizes with gemcitabine to inhibit cell proliferation and induce apoptosis in P a C a cells with significant modulation of key cancer regulators including PARP , VEGF , MMP s, IL s, caspases, and NF ‐κ B . In addition, biostatistical analyses, quantitative reverse transcription PCR data, and in silico modeling using T arget S can5, P ic T ar, and DNA intelligent analysis, micro T ‐ V . B 4 database showed that these two agents modulated a number of micro RNA s (mi R ‐21, mi R ‐196a, mi R ‐495, mi R ‐605, mi R ‐638, and mi R ‐453) linked to various canonical oncogenic signaling pathways. Conclusion We identified garcinol‐specific mi RNA biomarkers that sensitize P a C a cells to gemcitabine treatment, thus attenuating the drug‐resistance phenotype. These results prompt further interest in garcinol and gemcitabine combination strategy as a drug modality to improve treatment outcome in patients diagnosed with P a C a.