Table 2.
Activation/suppression of Nrf2 signaling and its association with DOX resistance/sensitivity.
| Cancer Type | Signaling Network | Compound/Agent | Nrf2 Expression | Remarks | Refs |
|---|---|---|---|---|---|
| Breast cancer | P62/Nrf2 | – | Up-regulation | Reducing oxidative stress Mediating DOX resistance Promoting colony formation and migration capacities Improving cancer stem cell features |
[216] |
| Breast cancer | Cul3/Nrf2 | – | Down-regulation | Association of Cul3 with Nrf2 depletion Inducing oxidative stress Increasing DOX sensitivity |
[231] |
| Breast cancer | PI3K/Nrf2/MRP1 | Vielanin P | Down-regulation | Inhibiting PI3K/Nrf2 axis Suppressing MRP1 expression Promoting DOX sensitivity |
[182] |
| Breast cancer | Nrf2/HSP70 | Parthenolide | Down-regulation | Reducing expressions of Nrf2 and HSP70 Enhancing DOX sensitivity of breast cancer cells |
[176] |
| Breast cancer | Nrf2/HO-1 Nrf2/MDR1 |
Luteolin | Down-regulation | Enhancing number of cancer cells undergoing cell death Increasing cytotoxicity of DOX Down-regulation of Nrf2 and subsequent inhibition of its downstream targets HO-1 and MDR1 |
[202] |
| Breast cancer | Nrf2/HO-1 Nrf2/NQO1 |
Wogonin | Down-regulation | Impairing cellular defense systemNrf2 signaling inhibition Down-regulation of HO-1 and NQO1 Increasing DOX cytotoxicity towards cancer cells |
[195] |
| Breast cancer | HER2/Nrf2 | – | Up-regulation | Conferring drug resistance Enhancing activities of antioxidant enzymes such as GSTA2, GSTP1 and HO-1 |
[232] |
| Breast cancer | Nrf2/p62 | Pseudomonas aeruginosa mannose-sensitive hemagglutinin | Down-regulation | Inhibiting Nrf2 signaling and its downstream target p62 Increasing DOX sensitivity Impairing cancer growth |
[190] |
| Hepatocellular carcinoma | MiRNA-101/Nrf2 | Apigenin | Down-regulation | Enhancing miRNA-101 expression Inhibiting Nrf2 signaling by binding to 3/-UTR Enhancing DOX sensitivity |
[186] |
| Hepatocellular carcinoma | PI3K/Akt/Nrf2 | Apigenin | Down-regulation | Reducing mRNA and protein levels of Nrf2 via PI3K/Akt inhibition Reducing cell proliferation Inducing apoptosis Promoting DOX sensitivity |
[189] |
| Liver cancer | Nrf2/ABCB1 | – | Up-regulation | Nrf2 overexpression occurs in hypoxic conditions Reducing apoptosis and DNA damage Inducing DOX resistance ABCB1 up-regulation |
[207] |
| Different cancers | MRTF-A/Nrf2 | – | Up-regulation | Reducing apoptosis Triggering DOX resistance |
[221] |
| Different cancers | – | – | Down-regulation | SiRNA is a powerful in Nrf2 down-regulation Inhibiting activities of ABCC3, ABCC4 and ABCG2 Enhancing DOX sensitivity |
[212] |
| Different cancers | PI3K/Akt/Nrf2 ERK/Nrf2 |
Chrysin | Down-regulation | Suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 signaling pathwaysNrf2 down-regulation and inhibiting its downstream targets HO-1 Enhancing DOX sensitivity |
[181] |
| Ovarian cancer | ALDH/Nrf2 | All-trans retinoic acid | Down-regulation | Promoting cancer stem features Enhancing colony formation capacity Mediating DOX resistance Suppressing ALDH/Nrf2 signaling by retinoic acid in reducing DOX resistance |
[191] |
| Ovarian cancer | – | – | Up-regulation | Overexpression of Nrf2 in DOX-resistant cancer cells Reducing tumor growth following Nrf2 down-regulation |
[233] |
| Ovarian cancer | – | – | Up-regulation | Obtaining DOX resistance via Nrf2 signaling and reducing cell death | [234] |
| Ovarian cancer | Nrf2/miRNA-206/c-MET/EGFR | – | Up-regulation | Reducing miRNA-206 expression Inducing expressions of c-MET and EGFR expressions Triggering DOX resistance |
[235] |
| Colorectal cancer | Nrf2/P-gp | – | Up-regulation | Enhancing P-gp expressions Reducing cell death Inducing DOX resistance |
[208] |
| Lung cancer | – | ML385 | Down-regulation | ML385 functions as an inhibitor of Nrf2 signaling Promoting DOX sensitivity |
[172] |
| Myeloid leukemia | Nrf2/HO-1 Nrf2/NQO1 |
Tritolide | Down-regulation | Enhancing drug sensitivity Apoptosis induction Suppressing Nrf2 and its downstream targets |
[203] |