Effect of fisetin supplementation on inflammatory factors and matrix metalloproteinase enzymes in colorectal cancer patients

Food Funct. 2018 Apr 25;9(4):2025-2031. doi: 10.1039/c7fo01898c.


A growing body of evidence indicates that inflammation is associated with tumorigenesis, metastasis and chemotherapeutic resistance in patients with colorectal cancer (CRC). Natural flavonoids are promising agents for inflammation-related tumor progression in patients with CRC. This study aimed to assess the efficacy of flavonoid fisetin supplementation on the inflammatory status and matrix metalloproteinase (MMP) levels in these patients. In this double-blind, randomized placebo-controlled clinical trial, 37 CRC patients undergoing chemotherapy were assigned to receive either 100 mg fisetin (n = 18) or placebo (n = 19) for seven consecutive weeks. The supplementation began one week before chemotherapy and continued until the end of the second chemotherapy cycle. Levels of interleukin (IL)-8, IL-10, high-sensitivity C-reactive protein (hs-CRP), MMP-7, and MMP-9 were measured in plasma using ELISA, before and after the intervention. The trial was registered at http://www.irct.ir (code: IRCT2015110511288N9). The participants were 55.59 ± 15.46 years old with 62.16% being male. After the intervention, the plasma levels of IL-8 and hs-CRP reduced significantly in the fisetin group (p < 0.04 and p < 0.01, respectively). Additionally, fisetin supplementation suppressed the values of MMP-7 levels (p < 0.02). However, significant changes were observed only in IL-8 concentrations in the fisetin group when compared with the placebo group (p < 0.03). The changes in the levels of other metabolic factors were not statistically significant. According to the results, fisetin could improve the inflammatory status in CRC patients, suggesting it as a novel complementary antitumor agent for these patients and warranting further studies.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • C-Reactive Protein / analysis
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • Dietary Supplements*
  • Double-Blind Method
  • Down-Regulation*
  • Female
  • Flavonoids / therapeutic use*
  • Flavonols
  • Humans
  • Interleukin-10 / blood
  • Interleukin-8 / blood*
  • Iran
  • Male
  • Matrix Metalloproteinase 7 / blood
  • Matrix Metalloproteinase 9 / blood
  • Middle Aged
  • Neoplasm Staging


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents, Phytogenic
  • CXCL8 protein, human
  • Flavonoids
  • Flavonols
  • IL10 protein, human
  • Interleukin-8
  • Interleukin-10
  • C-Reactive Protein
  • MMP7 protein, human
  • Matrix Metalloproteinase 7
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • fisetin