From:  Fisetin in malignant nervous system tumors: molecular insights and translational advances

 Summarizes key pharmacological studies examining fisetin’s biological effects in CNS tumor models.

ModelDose/FormulationMain findingsReference
U-138 MG glioblastoma cellsFisetin (FIS) & FIS-PLGA NPs; 25 µM and 50 µM

  • FIS and FIS-PLGA NPs showed cytotoxicity against U-138 MG cells and induced apoptosis.

  • At 25 µM, fisetin induced apoptosis (42.05 ± 2.30%) without significant cell cycle arrest.

  • However, at 50 µM, fisetin induced apoptosis in 73% of cells and statistically induced cell cycle arrest.

[45]
LN229 glioblastoma cells40–80 µM

  • Fisetin induced DNA damage and the induction of apoptosis.

  • Increased temozolomide cytotoxicity and exhibited senolytic activity.

[46]
T98G glioblastoma cells1–500 µM

  • Fisetin (IC50: 93 µM at 24 h; 75 µM at 48 h) showed an antiproliferative effect on T98G glioma cells.

  • Fisetin (IC50: 270 µM at 24 h; 90 µM at 48 h) showed an antiproliferative effect on BEAS-2B cells.

  • Fisetin at 25 and 50 µM showed upregulation of CASP3/8/9/BAX and downregulation of BCL-2/survivin.

[47]
GBM8401 glioma cellsFisetin (10–40 µM)

  • Fisetin blocked migration/invasion; repressed ADAM9 protein/mRNA through the maintenance of phosphorylation of ERK1/2.

  • U0126/siERK counteracted the inhibitory effect.

[48]
U-87 MG glioblastoma cells; EA.hy926 endothelial cellsFisetin + cisplatin co-loaded liposomes (DOPC/chol/PEG, ~ 1.7% fisetin, ~ 0.8% cisplatin loading); fisetin-loaded liposomes (1.2 mg/mL fisetin)

  • Fisetin exhibited cytotoxicity against U-87 MG glioblastoma cells (IC50 = 44 ± 32 µM after 48 h).

  • Co-loaded liposomes showed no synergism [combination index (CI) = 1.1 at 24 h and 48 h], but improved drug delivery and reduced toxicity compared to free drugs.

  • Co-encapsulation maintained antiangiogenic (morphological alterations, reduced IC50 in endothelial cells), additive cytotoxic (IC50 of cisplatin equivalents 6–15 µM), and sustained release, which is desirable in treating gliomas.

[49]
BV2 cells; Spinal Cord Injury (SCI) Sprague-Dawley Rat ModelFisetin (25–50 µM)
Fisetin-treated; fisetin (40 mg/kg) + autophagy inhibitor [chloroquine (20 mg/kg)] (oral dose)

  • Fisetin enhanced autophagy and suppressed apoptosis.

  • Decreased inflammation at the injury site.

  • Activation of AMPK and inhibition of mTOR reduced apoptosis and neuroinflammation.

  • Fisetin improved recovery of neurological function by enhancing autophagic activity, reducing neuronal apoptosis, and lowering pro-inflammatory markers (IL-6, TNF-α).

  • Autophagy-related pathways involving AMPK and mTOR were activated in response to fisetin.

[50]
Return to article view

CNS: central nervous system; PLGA: poly(lactic-co-glycolic acid); NPs: nanoparticles; IC50: half-maximal inhibitory concentration; ADAM9: A disintegrin and metalloproteinase 9; ERK: extracellular signal-regulated kinase; DOPC: 1,2-dioleoyl-sn-glycero-3-phosphocholine; PEG: polyethylene glycol; AMPK: AMP-activated protein kinase; mTOR: mechanistic (mammalian) target of rapamycin; IL-6: interleukin-6; TNF-α: tumor necrosis factor-alpha.