2-Methoxyestradiol does not inhibit superoxide dismutase

被引:63
作者
Kachadourian, R
Liochev, SI
Cabelli, DE
Patel, MN
Fridovich, I
Day, BJ
机构
[1] Natl Jewish Med & Res Ctr, Dept Med, Denver, CO 80206 USA
[2] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27708 USA
[3] Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA
关键词
2-methoxyestradiol; 2-hydroxyestradiol; superoxide; superoxide dismutase; aconitase; lactate dehydrogenase; human leukemia HL-60 cells;
D O I
10.1006/abbi.2001.2455
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2001 Academic Press.
引用
收藏
页码:349 / 353
页数:5
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