Table 2.
Anti-cancer activity and molecular targets modulated by genistein.
| Cancer | Cell Line | Genistein Concentration | Molecular Targets | Activity by Which Anti-Cancer Is Achieved | References |
|---|---|---|---|---|---|
| Breast | MCF-7 | 50 µM | NF-κB, AKT, BRCA1, BRCA2, HER2, EGFR, PDGFR, LRP, Abl | ↓ HER2 expression, apoptosis ↑ suppressor proteins | [69,70,71] |
| MDA-MB-231 | 30 µM | NF-κB, AKT, p21WAF1/CIP1, G1 Phase | ↓ phosphorylation of AKT and ↑ NF-κB DNA-binding activity, MDM-2-mediated degradation of p53, and p21WAFI | [72,73,74] | |
| Liver | HepG2 | 10–20 µM | TGF-β, NFAT1, FAK, EGFR, G2/M phase, NF-κB, MAPK, PI3K/AKT | Cell cycle arrest, ↓migration, MAPK, PI3K/AKT signaling pathways and apoptosis | [75] |
| Bel-7402 | 10 μg/mL | p125FAK, G0/G1 and G2/M phase | ↑ cell cycle arrest in the G0/G1 and G2/M phase, ↓ p125FAK | [75,76] | |
| HuH-7 | 20 µM | Caspase -3, -6, -7, -8, -10, MMP-9, NF-κB, MAPK/AP-1 and PI3K/AKT | ↑ apoptosis, fragmentation of DNA, ↓ NF-κB activity | [77,78] | |
| Hep3B | 15–25 µM | p38 MAPK, caspase, NF-κB, p53, AMPK | AMPK-mediated anti-inflammation and pro-apoptosis, ↓ TNF and IL-6, apoptosis, fragmentation of DNA, ↑ endoplasmic reticulum stress and mitochondrial insult | [76,78,79,80] | |
| SMMC-7721 | 10–20 µM | Caspase, NF-κB, G2/M phase, TGF-β, MAPK/AP-1, PI3K/AKT, p53 | Apoptosis, ↓ of NF-κB activity, ↑ cell cycle arrest in the G2/M phase | [81,82,83] | |
| Lung | A549 | 25–50 µM | EGFR, NF-κB, G2/M, miR-27a, MET and EGFR | Cell cycle arrest, apoptosis, G2 phase arrest, ↓MET protein expression levels, ↑ apoptosis via miR-27a and MET signaling pathways | [84,85,86] |
| H446 | 25 µM | FoXM1, Cdc25B, cyclin B, survivin | ↓ FoXM1, Cdc25B, cyclin B and survivin, ↑ apoptosis. | [81] | |
| Gastric | BGC-823 | 25 µM | Bcl-2, BAX, NF-κB, COX-2, G2/M, caspase-3, AKT | Apoptosis, ↓ Bcl-2, cell proliferation, G2/M Phase arrest, breakdown of caspases | [84,87,88] |
| SGC-7901 | 10–20 μg/mL | ERK1/2 (MAPK1/3) PI3K/AKT, PTEN, Ser642, Wee1, Cdc2/Cdk1, Thr15 | ↓tyrosine-specific protein kinases, phosphorylation of EP300 by inhibiting the activity of MAPK1, ↑ apoptosis | [89,90,91] | |
| Colon | DLD-1 cell line | 75 µM | Nuclear β-catenin, phospho-β-catenin, sFRP2, WNT pathway | ↓ β-catenin-mediated WNT signaling through increasing sFRP2 gene | [92] |
| SW480 | 10 µM | p21, cyclin D1, c-MYC, DKK1 | ↑ mRNA and DKK1 protein levels, ↓ cell proliferation, Induce histone acetylation | [93,94] | |
| HT29 | 60–120 µM | G2/M and S phases, p21WAF1, Bax/Bcl-2, phase, FOXO3 | G2/M phase cell cycle arrest, ↑ apoptosis through Bcl-2 family proteins, p21WAF1 during the cell cycle | [95,96] | |
| HCT116 | 25–50 µmol/L | Metalloproteinase, VEGF3, FOXO3, p53, PI3K/AKT, G2/M phase | Silencing of p53-determined activity of FOXO3, induce G2/M phase cell cycle arrest and apoptosis, ↓ MMP-2and Fms-related tyrosine Kinase 4. | [97,98] | |
| SW1116 | 10–30 µg/mL | G2/M Phase, PTKs, topoisomerase-II, PG/GAG | Cell cycle arrest in G2/M phase, ↓ protein tyrosine kinases and topoisomerase II, affects the synthesis of PG/GAG and ↓ cell proliferation | [99,100] |
Abbreviations: Abl: Ableson leukemia oncogene cellular homolog; AMPK: adenosine monophosphate-activated protein kinase; BAX: BCL2-associated X protein; Bcl-2: B-cell lymphoma 2; BRCA1, BRCA2: breast cancer gene; caspase: cysteine aspartic acid specific protease; Cdc2/Cdk1: cell division control protein; Cdc25B: cell division cycle 25B; c-MYC: C- myelocytoma; DKK1: dickkopf WNT signaling pathway inhibitor 1; EGFR: epidermal growth factor receptor; ERK1/2: extracellular signal-regulated kinases 1 and 2; FAK: focal adhesion kinase; FoXM1: forkhead box protein M1; FOXO3: forkhead box O3; HER2: human epidermal growth factor receptor 2; LRP: LDL-receptor-related protein; MAPK/AP-1: mitogen-activated protein kinase; miR-27a: microRNA-27a; MMP-9: matrix metalloproteinase 9; NFAT1: nuclear factor of activated T cells 1; NF-κB: nuclear factor kappa B; p125FAK: focal adhesion kinase; p21Waf1: cyclin-dependent kinase inhibitor 1; p53: phosphoprotein p53; PDGFR: platelet-derived growth factor receptor; PG/GAG: proteoglycans/glycosaminoglycans; PI3K/AKT: phosphatidylinositol-3-kinase and protein kinase B; PTEN: protein tyrosine phosphatase; PTKs: protein tyrosine kinases; sFRP2: secreted frizzled related protein 2; TGF-β: transforming growth factor beta; VEGF3: vascular endothelial growth factor 3; Wee1: small cell protein, a mitotic inhibitor kinase; WNT: Wingless/integrated.