Table 4 FOXO1 and treatment opportunities in glioma
Treatment | Cancer type | Drug type | Target genes | Role of FOXO1 | Effect on FOXO1 | Model | Description |
|---|---|---|---|---|---|---|---|
Progesterone [144] | GBM | Pleiotropic neurosteroid hormone | [EGFR]/PI3K/Akt/mTOR | NA | ↓↑ Time and dose-dependent | In vitro/In vivo | • ↓Tumor proliferation, angiogenesis, apoptosis |
Urolithin A [153] | GBM | Natural product | ERK/AKT/Sirt1-FOXO1 | TS | ↑ | In vitro/In vivo | • ↓Proliferation, migration and invasion • Sirt1 induces FOXO1 expression |
Curcumin [169] | GBM | Natural product | CDK1/FOXO1 | TS | ↑ | In vitro | • ↓Cell viability and proliferation • ↑G2/M cell cycle arrest and apoptosis |
Caffeine [170] | GBM | Natural product | FOXO1/Bim1 | TS | ↑ | In vitro | • ↓Cell proliferation and survival • ↑Subcellular localization of FOXO1 |
Xihuang pill [139] | GBM | Chinese herbal formula | ROS/Akt/mTOR/FOXO1 | TS | ↑ | In vitro | • ↓Cell growth • Arrested cell cycle • ↑Apoptosis |
PI-103 + γIR [136] | GBM-SCs with functional p53 | Dual PI3K/mTOR inhibitor | FOXO1 | Oncogene | ↓ | In vitro | • ↓Stem and progenitor cell markers as well as of FOXO1 |
Fenofibrate [171] | GBM | Fibric acid derivative (lipid lowering drug) | FOXO1/p27kip | TS | ↑ | In vitro | • ↓Cell proliferation • ↑G0/G1 arrest |
Endothelial-monocyte activating polypeptide-II (EMAP-II) [167] | GBM stem cells | Tumor-derived cytokine | PI3K/Akt/FOXO1/Atg2B | TS | low dose ↑ High dose ↓ | In vitro/In vivo | • ↓Tumor growth • ↑Cell cycle arrest • No effect on apoptosis • ↑Autophagy via PI3K/Akt/ FOXO1/ Atg2B axis |
Zerumbone [172] | GBM | Sesquiterpenoid natural product | Akt/FOXO1 | TS | ↑ | In vitro | • ↑Cell apoptosis through Akt inactivation and FOXO1 dephosphorylation |
Trifluoperazine (TFP) [173] | SHG44 glioma cell line resistant to doxorubicin | Phenothiazine derivative (antipsychotic drug) | FOXO1 | TS | ↑ | In vitro/In vivo | • Overcomes DOX resistance in SHG44/DOX cells via restoration of the nuclear FOXO1 |
NS1619 [168] | Rat brain glioma (C6) model | Calcium-activated potassium channel (Kca channel) activator | ROS/PI3K/PKB/FOXO1/ Caveolin-1 | TS | ↑ time dependent | In vitro/In vivo | • NS1619 increases the permeability of blood-tumor barrier due to caveolin-1 and FOXO1 expression |
AU-15330 [174] | Diffuse intrinsic pontine gliomas | Degrader of the SWI/SNF ATPase subunits, | FOXO1 | Oncogene | ↓ | In vitro | • Suppression of FOXO1 resulted in cell death in H3.3K27M cells |
Denbinobin [175] | GBM | Phenanthraquinone derivative (natural product) | IKKa/Akt/FOXO1/Caspase-3 | TS | ↑ | In vitro | • By FOXO1 dephosphorylation, leading to cell apoptosis |
AS1842856 [176] | GBM | A small molecule inhibitor that inactivates unphosphorylated FOXO1 | FOXO1 | Oncogene | ↓ | In vitro | • ↓Colony formation • ↑Apoptosis |