Naringenin inhibits migration of bladder cancer cells through downregulation of AKT and MMP‑2

Mol Med Rep. 2014 Sep;10(3):1531-6. doi: 10.3892/mmr.2014.2375. Epub 2014 Jul 14.

Abstract

Bladder cancer is one of the causes of cancer‑related death and has a high mortality rate due to its metastatic ability. Naringenin, a bioactive compound predominantly found in citrus fruits, exhibits several cellular functions, including anti‑oxidant, ‑lipidemia and ‑cancer abilities. However, the effects of naringenin on bladder cancer cells are yet to be elucidated. The present study investigated the molecular mechanisms underlying the effects of naringenin on the migration of TSGH‑8301 bladder cancer cells. Treatment with naringenin at doses ranging between 0 and 300 µM over a period of 24 h was found to reduce cell viability. Furthermore, zymography and western blot analysis revealed that naringenin reduced the expression of matrix metalloproteinase (MMP)‑2 in a dose‑dependent manner, and repressed its activity. Naringenin also reduced TSGH‑8301 cell migration in a concentration‑dependent manner, as evidenced by wound healing and Transwell® assays. In addition, naringenin was found to inhibit AKT activity and block the nuclear translocation of nuclear factor κ‑light‑chain‑enhancer of activated B cells. In conclusion, the findings of the present study show that naringenin is capable of inhibiting bladder cancer cell migration through the downregulation of the AKT and MMP‑2 pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Flavanones / pharmacology*
  • Humans
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • Urinary Bladder Neoplasms / metabolism

Substances

  • Flavanones
  • NF-kappa B
  • Proto-Oncogene Proteins c-akt
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • naringenin