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

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

Research output: Contribution to journalArticlepeer-review

153 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)942-948
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume296
Issue number4
DOIs
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • Apoptosis
  • Bcl-2, Mcl-1 and cytochrome c
  • Breast cancer
  • Lipoxygenase (LOX)

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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