Table 2.

Therapeutic Strategies for targeting SOD2.

Therapy	Treatment	Mode of Action	References
Epigenetic Drugs	Zebularine	Reverses SOD2 promoter methylation	[49]
	Tirchostatin A	Regulates histone methylation and acetylation	[51,114]
	Sodium butyrate
Adenoviral Vectors	Cu-Zn SOD/SOD2 adenoviral vectors combined with BCNU	Induces SOD expression to reduce cancer cell growth and increases survival	[119]
	SOD2 and TRAIL combination	Enhances SOD expression to stimulate cell apoptosis and reduce tumor growth	[120]
Topoisomerase inhibitors	Doxorubucin	Reduces cancer growth by binding to the topoisomerase enzymes and block topoisomerases 1 and 2	[154]
	Topotecan
Redox Cyclin Compounds	Motexafin gadolinium	Induces apoptosis by alteration in mitochondrial membrane potential, depletion of intracellular GSH and increased ROS production.	[155]
GSH Depleting Agents	Buthionine sulphoximine	Eliminates GSH from the cells by blocking GPx and accumulates ROS production Oxidative inactivation of H-Ras and NF-kB Oxidative damage of mitochondria Induces apoptosis	[126,127,128,133]
	β-phenylethyl isothiocyanates (PEITC)
SOD2 inhibitors	2-methoxyestradiol	Blocks both manganese and copper, zinc superoxide dismutases and reduces cancer growth	[156]
Catalase	3-amino-1,2,4, triazole	Reduces CAT activity Enhances intracellular H2O2 levels Decreases GPx activity	[157]
Anti-fungal Antibiotic	Rapamycin	Inhibits cell proliferation Stimulates apoptosis Blocks mTORC1 and activates Akt to promote chemoresistance	[129,130,131,132,133,134]
Proteosome inhibitor	MG132	Reduces FOXM1 expression to induce apoptosis	[137,138,139]
Thiazole Antibiotic	siomycin-A
Natural Products	Curcumin	Conserves SOD2 expression Delays bile acid-induced esophageal injury and cancer progression	[147,148]
	Astaxanthin	Inhibits expression of NF-κB, TNF-α, and IL-8 to induce ROS/reactive nitrogen species scavenging	[149]
	Ginger	Inhibits oxidative stress and cancer growth by stimulating SOD, CAT, GPx, glutathione-S-transferase, and glutathione reductase activities	[150]
	Oroxylin A	Induces SOD2 gene expression Inhibits glycolysis Suppresses tumor growth	[151]
	Protandim	Stimulates SOD and CAT activities Reduces tumor growth	[153]

2-ME: 2-methoxyestradiol; Akt: protein kinase B; BCNU: 1,3-bis(2-chloroenthyl)-1-nitrosurea; CAT: catalase; Cu-Zn: copper–zinc; FOXM1: forkhead box M1; GPx: glutathione peroxidases; GSH: glutathione; IL: interleukin; mTORC1: mammalian target of rapamycin complex 1; NF-kB: nuclear factor-kappa B; PEITC: phenylethyl isothiocyanates; ROS: reactive oxygen species; TNF: tumor necrosis factor; TRAIL: TNF-related apoptosis-inducing ligand.