Interactions between dietary flavonoids apigenin or luteolin and chemotherapeutic drugs to potentiate anti-proliferative effect on human pancreatic cancer cells, in vitro

Food Chem Toxicol. 2013 Oct;60:83-91. doi: 10.1016/j.fct.2013.07.036. Epub 2013 Jul 18.


The objectives were to assess the potential of dietary flavonoids apigenin (Api) and luteolin (Lut) to enhance the anti-proliferative effects of chemotherapeutic drugs on BxPC-3 human pancreatic cancer cells and to investigate the potential molecular mechanism of action. Simultaneous treatment or pretreatment (0, 6, 24 and 42 h) of flavonoids and chemotherapeutic drugs at various concentrations (0-50 μM) were assessed using the MTS cell proliferation assay. Simultaneous treatment with either flavonoid (13, 25 or 50 μM) and chemotherapeutic drugs 5-fluorouracil (5-FU, 50 μM) or gemcitabine (Gem, 10 μM) for 60 h resulted in mostly less-than-additive effects (p<0.05). Pretreatment for 24h with 13 μM of either Api or Lut, followed by Gem for 36 h was optimal to inhibit cell proliferation. Pretreatment of cells with 11-19 μM of either flavonoid for 24h resulted in 59-73% growth inhibition when followed by Gem (10 μM, 36 h). Lut (15 μM, 24h) pretreatment followed by Gem (10 μM, 36 h), significantly decreased protein expression of nuclear GSK-3β and NF-κB p65 and increased pro-apoptotic cytosolic cytochrome c. Pretreatment of BxPC-3 human pancreatic cancer cells with low concentrations of Api or Lut effectively aid in the anti-proliferative activity of chemotherapeutic drugs.

Keywords: -Roswell Park Memorial Institute; -apigenin; -nuclear factor kappa B; -oxaliplatin; 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; 5-FU; 5-fluorouracil; Api; Apigenin; Chemotherapeutic drugs; Cis-; GSK-3β; GSK-3β-; Gem-; Lut-; Luteolin; MTS; NF-κB; Oxa; PES-; Pancreatic cancer cells; RPMI; cisplatin; gemcitabine; glycogen synthase kinase-3β; luteolin; phenazine ethosulfate.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apigenin / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Drug Synergism
  • Fluorouracil / pharmacology
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Luteolin / pharmacology*
  • Pancreatic Neoplasms / metabolism
  • Signal Transduction
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism


  • Antineoplastic Agents
  • Transcription Factor RelA
  • Deoxycytidine
  • Apigenin
  • gemcitabine
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Luteolin
  • Fluorouracil