Table 1.
Studies on the use of various MIF inhibitors in BC.
| Author(s) | MIF inhibitors | Target/Binding mode | In vitro model | In vivo model | Main findings | Country |
|---|---|---|---|---|---|---|
| Cotzomi-Ortega et al 76 | ISO-1 | Tautomerase site/competitive | 66cl4, 67NR or 4T1 cell lines | — | Cell death, prevention of malignancy promotion | Mexico |
| Charan et al 57 | CPSI-1306 | Tautomerase site/competitive | MDA-MB-468, MDA-MB-231, and MVT-1 | Female FVB, C57BL/6, and NOD/SCID/IL-2 gamma (NSG) mice | Growth inhibition and apoptosis induction in TNBC cells. Activation of pro-apoptotic proteins and suppression of cell survival markers. Inhibition of tumor growth along with progression and metastasis in a mouse model |
United States |
| Charan et al 77 | CPSI-1306 | Tautomerase site/competitive | — | A xenograft and MIF knockout mouse model | Diminished infiltration of MDSCs and increased infiltration of CD8+ T cells in tumor and spleen. Reduction of GCSF, GMCSF, IL-2 and IL-4, cytokines, and chemokines |
United States |
| Das et al 78 | CPSI-1306 | Tautomerase site/competitive | MDA-MB 468 and MDA-MB 231 | MVT-1 orthotopic mouse model | Decreased AKT, apoptosis, and low cell viability. Reduction in tumor growth and lung metastasis |
United States |
| Das et al 79 | 4-IPP | Terminal nucleophilic proline/irreversible | MDA-MB-231 | — | Apoptosis, reduced induction of chemoresistance, and AKT phosphorylation | India |
| Simpson et al 72 | SFN | Terminal nucleophilic proline/irreversible | — | A female Balb/c 4T1 mouse model | Decreased MIF expression and reduced induction of monocytic MDSCs | United States |
| Delgado et al 80 | Epicatechin | Terminal nucleophilic proline/irreversible | MCF-7 | — | Anti-proliferative activity | Spain and Portugal |
| Thabet and Moustafa 89 | Ebselen | Cys-80/allosteric | MCF-7 | — | Decrease in VEGF level and proliferative capacity. Lower expression of NF-κB, TNF-α, IL-2, INF-γ, and TGF-β. Increased expression of granzyme-B, TRAIL, and IL-10 genes |
Egypt |
| Kumar et al 93 | Epoxyazadiradione | Asn-105 and Asn-102/allosteric | MDA-MB-231 and MCF-7 | An orthotopic NOD/SCID mice model | Apoptosis induction PI3K/AKT inhibition and cell survival. Inhibition of migration and angiogenesis through factors such as COX-2, OPN, VEGF, and MMP-9. Reduction of breast tumor growth and angiogenesis in a mouse model |
India and United States |
| Lakshmi et al 94 | Epoxyazadiradione | Asn-105 and Asn-102/allosteric | MDA-MB-231 | — | Arrest in G2/M by downregulation of cyclin A2/cdk2 and apoptosis. Decreased NF-κB, EGFR, MMP-9, and fibronectin. Inhibition of migration and colony formation. Interference in cellular metabolism |
India |
| Verjans et al 25 | Anti-MIF and anti-CD74 Abs | MIF/CD74 disruption | MDA-MB-231 and MDA-MB-468 | — | Prevention of cell proliferation | Germany |
| Schulz et al 99 | 17AAG | HSP90 inhibitor | — | ErbB2 transgenic model of HER2-positive BC | Reduction of MIF and tumor growth | Germany |
| Jhaveri et al 101 | Ganetespib | HSP90 inhibitor | — | Patients with MBC in a phase II clinical trial | Potent inhibitory effects on oncoproteins associated with BC pathogenesis | United States |
| Fujita et al 103 | Aza-resveratrol | Tautomerase activity of MIF | MCF-7 | — | Anti-proliferative effects | Japan |
| Simpson et al 72 | Anti-MIF shRNA | Disruption of protein synthesis | 4T1 | A balb/c mouse model | Reduction in primary tumor growth and low number of lung micrometastases. Drop in MDSCs |
United States |
| Charan et al 57 | MIF-specific siRNA (si-MIF) | Disruption of protein synthesis | MDA-MB-468 and MDA-MB-231 | — | Increased apoptosis. Decline in colony forming ability, migration, and wound healing capacity |
United States |
| Zhang et al 104 | Glucan-based cationic nanoparticle containing siRNA against MIF (siMIF-NP) | Disruption of protein synthesis | MDA-MB-231 and 4T1 | A 4T1 mouse model | Lower cell proliferation and higher apoptosis. Diminished immunosuppression and elevated number of infiltrating CD8+ T cells in treated tumors |
United States |
| Wu et al 64 | MIF-specific siRNA (si-MIF) | Disruption of protein synthesis | MCF-7 | A xenograft mouse model with MCF-7 | Decreased cell proliferation and survival. Autophagy induction Suppression of tumor growth in nude mice |
United States |
Abbreviations: GCSF, granulocyte colony-stimulating factor; GMCSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; MDSC, myeloid-derived suppressor cell; MIF, migration inhibitory factor; MMP, matrix metalloproteinase; TNBC, triple-negative breast cancer; VEGF, vascular endothelial growth factor.