TY - JOUR T1 - Fisetin Enhances the Cytotoxicity of Gemcitabine by Down-regulating ERK-MYC in MiaPaca-2 Human Pancreatic Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 3527 LP - 3533 DO - 10.21873/anticanres.12624 VL - 38 IS - 6 AU - NAYOUNG KIM AU - MIN-JUNG KANG AU - SANG HYUB LEE AU - JUN HYUK SON AU - JI EUN LEE AU - WOO HYUN PAIK AU - JI KON RYU AU - YONG-TAE KIM Y1 - 2018/06/01 UR - http://ar.iiarjournals.org/content/38/6/3527.abstract N2 - Background: Pancreatic cancer is a highly lethal malignancy with a poor prognosis. This study was set up to investigate the combined effect of gemcitabine and fisetin, a natural flavonoid from plants, on human pancreatic cancer cells. Meterials and Methods: Cytotoxic effect of fisetin in combination with gemcitabine on MiaPaca-2 cells was evaluated by the MTT assay, caspase 3/7 assay and propidium iodide/Annexin V. Extracellular signal-regulated kinase (ERK)-v-myc avian myelocytomatosis viral oncogene homolog (MYC) pathway was investigated by western blotting and quantitative real-time polymerase chain reaction. Results: Combination treatment with fisetin and gemcitabine inhibited the proliferation of pancreatic cancer cells within 72 h and induced apoptosis, as indicated by activation of caspase 3/7. Fisetin down-regulated ERK at the protein and mRNA levels, and reduced ERK-induced MYC instability at the protein level. Conclusion: Fisetin sensitized human pancreatic cancer cells to gemcitabine-induced cytotoxicity through inhibition of ERK-MYC signaling. These results suggest that the combination of fisetin and gemcitabine could be developed as a novel potent therapeutic. ER -