The mechanisms of lipoxygenase inhibitor-induced apoptosis in human breast cancer cells.

Wei-Gang Tong, Xian-Zhong Ding, Thomas E Adrian

Journal: Biochemical and biophysical research communications 2002;296(4):942-8

PMID: 12200139

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Department of Surgery, Gastrointestinal Oncology Laboratories, Northwestern University Medical School, Chicago, IL 60611, USA.

DOI: 10.1016/s0006-291x(02)02014-4