Table 1.
Summary of the Anticarcinogenic Effects of Fisetin in In-Vitro Studies
| Target organ | In-vitro studies | References |
|---|---|---|
| Lung | Decreased cancer cell viability and clonogenecity, increased PTEN, decreased PI3-K and Akt phosphorylation, activated TSC and AMPK, decreased phosphorylation and activation of mTOR, decreased phosphorylation of p70S6K1, eIF-4E, and 4E-BP1, inhibited mTORC constituents such as Rictor, Raptor, GβL, and PRAS40 | 27 |
| Inhibited adhesion, migration, and invasion via inhibition of ERK1/2, downregulated MMP-2, uPA, NF-κB, and AP-1 | 38 | |
| Colon | Decreased cancer cell viability | 35, 61 |
| Induced cell cycle arrest, inhibited cdk-4 and 6 | 41 | |
| Induced cytotoxicity via securin degradation independent of p53 | 72 | |
| Induced apoptosis via extrinsic and intrinsic pathways, activated p53, increased TRAIL protein levels | 39, 61 | |
| Inhibited EGFR and NF-κB, decreased COX2 and PGE2, inhibited Wnt/β-catenin signaling, downregulated TCF-4, decreased cyclin D1 and MMP-7 | 61 | |
| Enhanced radiosensitivity of p53-mutant colon cancer cells, augmented radiation-induced G2/M arrest and apoptosis | 9 | |
| Prostate | Antiproliferative | 20 |
| Induces cell cycle arrest, induced cell death through apoptosis, and autophagy | 29, 62 | |
| Augmented TRAIL-mediated cytotoxicity, increased TRAIL protein expression, inhibited NF-κB | 67 | |
| Induced autophagy, activated AMPK, inhibited mTOR activity, mTOR complex formation, inhibited mTOR targets rpS6, eIF4B, and 4EBP1, suppressed Cap-dependent translation, Akt phosphorylation | 62 | |
| Inhibited adhesion, migration, and invasion, suppressed PI3K/Akt/JNK signaling downregulated MMPs | 11 | |
| Inhibited AR transactivation of target genes, including PSA, through interaction with AR | 30 | |
| Pancreas | Inhibited cell growth, induced apoptosis, inhibited invasion, suppressed DR3-mediated NF-κB activation, decreased MMP-9 | 48 |
| Melanoma | Decreased cell viability, induced G1-phase arrest, downregulated Wnt protein and its coreceptors, increased Wnt inhibitors Dickkopf and WIF-1, decreased nuclear β-catenin levels, downregulated β-catenin targets such as c-myc, Brn-2 and MITF | 65 |
AMPK, AMP-activated protein kinase; AR, androgen receptor; COX, cyclooxygenase; DR, death receptor; EGFR, epidermal growth factor receptor; eIF4B, eukaryotic initiation factor 4B; ERK1/2, extracellular signal-regulated kinase; MITF, microphthalmia-associated transcription factor; MMP, matrix metalloproteinase; NF-κB, nuclear factor-kappa B; PGE2, prostaglandin E2; PSA, prostate-specific antigen; PTEN, phosphatase and tensin homolog; TCF, transcription factor T-cell factor; TRAIL, TNF-related apoptosis-inducing ligand; uPA, urokinase plasminogen activator; WIF-1, Wnt inhibitory factor; XIAP, X-linked inhibitor of apoptosis.