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8437764 
Journal Article 
The mechanisms of lipoxygenase inhibitor-induced apoptosis in human breast cancer cells 
Tong, WG; Ding, XZ; Adrian, TE 
2002 
Yes 
Biochemical and Biophysical Research Communications
ISSN: 0006-291X
EISSN: 1090-2104 
296 
4 
942-948 
English 
Previous experimental studies have shown that high dietary fat intake is associated with mammary carcinogenesis. In the current study, the effect of 5-LOX or 12-LOX inhibitors on human breast cancer cell proliferation and apoptosis, as well as the possible mechanisms were investigated. The LOX inhibitors, NDGA, Rev-5901, and baicalein all inhibited proliferation and induced apoptosis in MCF-7 (ER+) and MDA-MB-231 (ER)) breast cancer cell in vitro. In contrast, the LOX products, 5-HETE and 12-HETE had mitogenic effects, stimulating the proliferation of both cell lines. These inhibitors also induced cytochrome c release, caspase-9 activation, as well as downstream caspase-3, caspase-7 activation, and PARP cleavage. LOX inhibitor treatment also reduced the levels of anti-apoptotic proteins Bcl-2 and Mcl-1 and increased the levels of the pro-apoptotic protein bax. In conclusion, blockade of both 5-LOX and 12-LOX pathways induces apoptosis in breast cancer cells through the cytochrome c release and caspase-9 activation, with changes in the levels of Bcl-2 family proteins. © 2002 Elsevier Science (USA). All rights reserved. 
Apoptosis; Bcl-2, Mcl-1 and cytochrome c; Breast cancer; Lipoxygenase (LOX)