Fisetin Enhances the Cytotoxicity of Gemcitabine by Down-regulating ERK-MYC in MiaPaca-2 Human Pancreatic Cancer Cells

Anticancer Research
Nayoung KimYong-Tae Kim

Abstract

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. 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. 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.

Citations

Jan 22, 2021·Food Science & Nutrition·Muhammad ImranFaqir M Anjum
Jun 17, 2021·Journal of Agricultural and Food Chemistry·Asifa KhanMohammad Askandar Iqbal
Jan 4, 2022·Cancer Biology & Therapy·Moein Ala

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