Table 1. Metabolic blockade-based anticancer treatments and their effect on metabolism or redox balance.
| Name | Type of tumor | Mechanism of action | Impact on redox and metabolism | Clinical stage | References |
|---|---|---|---|---|---|
| Etomoxir | Glioblastoma; leukemia | Inhibition of CPT1 | ROS elevation through NADPH and ATP depletion | Preclinical | 89 |
| 6-aminonicotinamide | Prostate cancer; head and neck carcinoma | Inhibition of 6-phosphogluconate dehydrogenase | ROS increase through NADPH and GSH decrease | Approved | 94, 97 |
| Buthionine sulfoximine | Breast cancer; acute limphoblastic leukemia; multiple myeloma | Inhibition of GSH neosynthesis mediated by glutamate cysteine ligase | ROS increase due to GSH depletion | Approved | 163, 168, 169 |
| Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide; compound 968 | B-cell lymphoma; acute myeloid leukemia; pancreatic cancer | Inhibition of glutaminase enzymes | Decreased intracellular GSH content and enhanced sensitivity to pro-oxidants | Approved | 108,109,110 |
| Arsenic trioxide | Small cell lung cancer; hepatocellular carcinoma; acute promyelocytic leukemia | Inhibition of mitochondrial respiration; cross-linking of thiols in redox-sensitive cysteines of GSH and antioxidant enzymes | Increased susceptibility to oxidative stress due to GSH oxidation and inactivation of Trx1, Trx2, Prx3 and Gpx2; decrease in ATP synthesis due to factor B inhibition | FDA approved | 22, 161, 163, 164 |
| Anthracyclines (doxorubicin, daunorubicin) | Colon carcinoma; breast cancer; neuroblastoma | Redox cycling and S-glutathionylation of mETC proteins; alteration of iron homeostasis | Increased ROS production due to Fenton's reaction and inhibition of the mETC complexes | FDA approved | 95 |
| Cisplatin | Non-small lung cancer; ovarian cancer; | Interference with the mETC activity; activation of the NADPH oxidases | Induction of intracellular and mitochondrial ROS production leading to lipid peroxidation, DNA damage and Ca2+ influx | FDA approved | 48,49,50,164 |
| Menadione | Pancreatic carcinoma; lung cancer | Triggering of redox cycling reactions; arylation of cellular thiols provoking GSH depletion | Increased ROS levels due to redox cycling; increased susceptibility to oxidation due to GSH decrease | Phase II | 165 |
| Metformin; phenformin | Melanoma; breast cancer; non-small lung cancer | Interference with mETC activity | Increased mitochondrial ROS production | Phase 0–II | 148, 149,150,153,154,155,156,157,158 |
Abbreviation: CPT1, carnitine palmitoyltransferase-1