Combined effect of chrysin and apigenin on inhibiting the development and progression of colorectal cancer by suppressing the activity of P38-MAPK/AKT pathway

IUBMB Life. 2021 May;73(5):774-783. doi: 10.1002/iub.2456. Epub 2021 Mar 15.


Either apigenin or chrysin alone has been found to exert anti-inflammatory and tumor suppressive effect. However, the combined effect of apigenin and chrysin on colorectal cancer (CRC) has not been fully clarified. We attempted to explore the effect of chrysin and apigenin on CRC and its related mechanism. SW480 and HCT-116 cells were treated with either apigenin or chrysin alone or two-drug combination at different doses of 5, 25, 50, 100 μM for optimal concentration determination. Then, we focused on the individual and combined effect of apigenin and chrysin on clonogenicity, apoptosis, metastasis-related behaviors of CRC cells by colony formation assay, cell scratch assay, flow cytometry, and transwell assay. The changes of the activation of P38-MAPK/AKT pathway were evaluated underlying apigenin and chrysin intervention, further after co-treated with P38-MAPK agonist anisomycin. Apigenin (25 μM) combined with chrysin (25 μM) were determined to be optimal. Treatment with the combination of apigenin (25 μM) and chrysin (25 μM) significantly reduced cell clone numbers, migration, and invasion ability, while increased the cell apoptosis in both CRC cell lines. The combined effect was higher than chrysin or apigenin alone. Meanwhile, p-P38 and p-AKT were significantly downregulated by chrysin and apigenin treatment. The tumor inhibitive effect of apigenin combined with chrysin was obviously reversed by adding P38 agonist, anisomycin. Apigenin (25 μM) combined with chrysin (25 μM) showed synergetic effect in inhibiting the growth and metastasis of CRC cells by suppressing the activity of P38-MAPK/AKT pathway.

Keywords: apigenin; cell scratch assay; cell viability; chrysin; colon cancer cells; colony formation; transwell.

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / pathology*
  • Anisomycin / pharmacology
  • Apigenin / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Clone Cells
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / pathology*
  • Drug Synergism
  • Flavonoids / pharmacology*
  • HCT116 Cells
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / physiology
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / physiology
  • Proto-Oncogene Proteins c-akt / physiology
  • Tumor Stem Cell Assay
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors


  • Flavonoids
  • Neoplasm Proteins
  • chrysin
  • Anisomycin
  • Apigenin
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases