2-methoxyestradiol does not inhibit superoxide dismutase.
It has been reported in the literature that the endogenous estrogen metabolite 2-methoxyestradiol (2-ME) inhibits both manganese and copper,zinc superoxide dismutases (Mn and Cu,Zn SODs) and that this mechanism is responsible for 2-ME's ability to kill cancer cells. In fact, as demonstrated using several SOD assays including pulse radiolysis, 2-ME does not inhibit SOD but rather interferes with the SOD assay originally used. Nevertheless, as confirmed by aconitase inactivation measurements and lactate dehydrogenase release in human leukemia HL-60 cells, 2-ME does increase superoxide production in these cells and is more toxic than its non-O-methylated precursor 2-hydroxyestradiol. Other mechanisms previously suggested in the literature may explain 2-ME's ability to increase intracellular superoxide levels in tumor cells.
Kachadourian
R
R
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Liochev
S I
SI
Cabelli
D E
DE
Patel
M N
MN
Fridovich
I
I
Day
B J
BJ
D000077584:2-Methoxyestradiol; D000154:Aconitate Hydratase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004837:Epinephrine / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D005649:Fumarate Hydratase / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D007202:Indicators and Reagents / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010617:Phenanthridines / Q000378:metabolism; D011485:Protein Binding; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D010617:Phenanthridines; D013778:Tetrazolium Salts; C059087:2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide; C058428:hydroethidine; D004958:Estradiol; D000077584:2-Methoxyestradiol; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D005649:Fumarate Hydratase; D000154:Aconitate Hydratase; D010100:Oxygen; D004837:Epinephrine