Table 2.
Anti-rheumatic drugs with possible ferroptosis-regulating effects found in different models.
| Drug | Cell line or animal model | Mechanisms regulating ferroptosis | Reference | ||
|---|---|---|---|---|---|
| Type | Name | Iron accumulation | Lipid peroxidation | ||
| Glucocorticoids | DXMS | HT1080 cells | Not known yet. | Upregulation of DPEP1 to reduce GSH to increase the sensitivity to ferroptosis | (74) |
| MC3T3-E1 cells; MLOY4 cells | Not known yet. | Upregulation of P53 to inhibit the expression of SLC7A11/GPX4 | (75) | ||
| NSAIDs | IND | GA mouse model | Not known yet. | Upregulation of GPx activity to reduce MDA levels | (57) |
| IBU | Glioblastoma cells | Not known yet. | Upregulation of Nrf2, GPX4 and SLC7A11 | (76) | |
| DMARDs | MTX | T cells | Not known yet. | Promotion of ROS production | (77) |
| HT22 cells | Promotion of iron accumulation; Upregulation of FTH1 and downregulation of NCOA4 |
ROS accumulation | (78) | ||
| SASP | Lymphoma cells | Not known yet. | Inhibition of System Xc- | (79) | |
| HCQ | LPS-treated monocytes | Not known yet. | Downregulation of ROS and MDA; upregulation of GSH and GPx | (80) | |
| CTX | Glioblastoma cells; breast cancer cells | Upregulation HMOX-1 to increase LIP | Not known yet. | (81) | |
| Biological agents | ADA+IKE/ ETN+IKE |
RA-FLSs | Not known yet. | Counteraction of TNF-induced cystine uptake and GSH synthesis to increase ferroptosis sensitivity | (39) |
| TCZ | RA-FLSs | Counteraction of IL-6-induced upregulation of LIP to decrease ferroptosis sensitivity | Not known yet. | (39) | |
| Anti-rheumatic | RES | RA-FLSs | Not known yet. | Activation of the Keap1-Nrf2 pathway | (82) |
| natural extracts | ICA | Synovitis cell model | Downregulation of TfR1 and NCOA4 | Upregulation of GPX4, SLC7A11, SLC3A2L and NRF2 | (38) |
| MC3T3-E1 osteoblast cells | Not known yet. | Attenuation of iron-induced ROS production | (68) | ||
| Iron overload mice | Attenuation of iron deposition | Not known yet. | (68) | ||
| QUR | OA mouse model | Not known yet. | Downregulation of ROS; upregulation of GSH and GPx | (83) | |
| BA | GA mouse model | Not known yet. | Upregulation of GPx activity to reduce MDA | (57) | |
| Other molecules | Gly | RA-FLSs | Methylation of GPX4 promoter; downregulation of FTH1 | Not known yet. | (41) |
ADA, adalimumab; BA, boswellic acid; CTX, cyclophosphamide; DMARDs, disease-modifying anti-rheumatic drugs; DPEP1, dipeptidase-1; DXMS, dexamethasone; ETN, etanercept; FLS, fibroblast-like synoviocyte; FTH1, ferritin heavy chain1; GSH, glutathione; HCQ, hydroxychloroquine; HMOX-1, heme oxygenase 1; IBU, ibuprofen; ICA, icariin; IKE, imidazole ketone Erastin; IND, indomethacin; Gly, glycine; LIP, LPS, lipopolysaccharide; MTX, methotrexate; NCOA4, nuclear receptor coactivator 4; NSAIDs, nonsteroidal anti-inflammatory drugs; PDAC, pancreatic ductal adenocarcinoma; QUR, quercetin; RES, resveratrol; ROS, reactive oxygen species; SASP,sulfasalazine; TfR1, transferrin receptor 1; TCZ, tocilizumab.