Mechanisms underlying GSH regulation of CSCs
| CSCs | Marker | GSH-related mechanism | Reference |
|---|---|---|---|
| Breast | ALDH＋, mammosphere |
Chemotherapy increases the expression levels of SLC7A11 and GCLM in a HIF-1-dependent manner | (36) |
| ALDH＋, mammosphere, CD44＋CD24−/low | DKK1 which is secreted by BCSCs increases the expression levels of SLC7A11 and inhibits ferroptosis | (44) | |
| CD44＋CD24− | SOD2K68Ac promotes the reprogramming of BCSCs by increasing the level of mitochondrial H2O2, which decreases GSH and stabilizes HIF-2α | (34) | |
| CD44＋CD24− (M-BCSCs) ALDH＋ (E-BCSCs) |
Inhibition of both GSH and thioredoxin antioxidant systems mitigate E-BCSCs, but not M-BCSCs. NAC promotes an E-to-M transition of BCSCs | (46) | |
| Pancreatic | CD133＋ | GSH synthesis and recycling-related genes are highly expressed in CSCs. GSH or NADPH depletion decreases self-renewal and CD133 expression | (18) |
| Colorectal | CD44＋, CD133＋, SP, sphere formation, and colony formation | CD44v8-10 stabilizes SLC7A11 in CSCs. mi-1297 which targets SLC7A11 mRNA is reduced in CSCs, increasing the level of GSH | (26) |
| Prostate | Sphere formation, ALDH＋ | Glutamine depletion decreases GSH levels and inhibits CSCs | (19) |
| Brain | Nanog＋, Musashi1＋, Sox2＋, Nestin＋ | (20) | |
| CD133＋, Sox2＋, Nestin＋ | Acidosis stress increases reduced GSH levels by promoting the pentose phosphate pathway | (21) | |
| Stomach | CD44＋ | CD44v8-10 increases GSH synthesis by interacting with SLC7A11 | (27) |
| Liver | CD44＋ | CD44 null ameliorates antioxidant capacity by decreasing GPX1 and thioredoxin but increasing GSH level | (22) |
| Lung | ALDH＋CD44＋CD133＋ | GSTP1 upregulates lung adenocarcinoma stemness under hypoxic conditions | (23) |
| AML | CD34＋CD38−CD123＋ CD45＋CD3−CD19−CellROXhigh | STAT3 promotes GSH synthesis by upregulating MYC and SCL1A5 | (24) |
| Bladder | CD44v9＋ | CD44v9 is correlated with poor outcomes in muscle-invasive bladder cancer patients. Sulfasalazine decreases GSH levels by modulating CD44v9-SCL7A11 system | (28) |
GSH: glutathione, CSCs: cancer stem cells, AML: acute myeloid leukemia. GCLM: glutamate-cysteine ligase modifier subunit, BCSCs: breast cancer stem cells, SOD2K68Ac: superoxide dismutase acetylation of lysine 68, NAC: