Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.60 (caspase-7)
 920 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The mechanisms of lipoxygenase inhibitor-induced apoptosis in human breast cancer cells. 1220 Jan 39

Several studies have suggested that high dietary fat intake, particularly essential fatty acids, is associated with pancreatic cancer development and growth. Our previous studies have demonstrated that blockade of either the 5-lipoxygenase (LOX) or 12-LOX pathway of arachidonic acid metabolism inhibited pancreatic cancer cell proliferation and induced apoptosis. This study investigated the underlying mechanisms for LOX inhibitor-induced apoptosis and the potential of LOX inhibitors as antipancreatic cancer agents using the athymic mice xenograft model. Apoptosis of pancreatic cancer cells induced by LOX inhibitors (including the nonselective LOX inhibitor nordihydroguaiaretic acid, the 5-LOX inhibitor Rev-5901, and the 12-LOX inhibitor baicalein) was confirmed by growth inhibition, annexin V binding, and terminal deoxynucleotidyl transferase-mediated nick end labeling assay in MiaPaCa-2 and AsPC-1 human pancreatic cancer cells. Expression of the antiapoptotic proteins Bcl-2 and Mcl-1 was significantly decreased after LOX inhibitor treatment while that of the proapoptotic protein bax was increased. LOX inhibitors also markedly induced the release of cytochrome c from mitochondria into the cytosol. Caspase-9, caspase-7, and caspase-3 but not caspase-8 were activated after treatment, concomitant with cleavage of the capase-3 substrate poly(ADP-ribose) polymerase. In vivo studies in the athymic mice xenograft model also confirmed the growth inhibitory effect and induction of apoptosis by these LOX inhibitors in pancreatic cancer. In conclusion, LOX inhibitors block pancreatic cancer cell proliferation and induce apoptosis through the mitochondrial pathway both in vivo and in vitro. LOX inhibitors are likely to be valuable for the treatment of human pancreatic cancer.
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PMID:Lipoxygenase inhibitors attenuate growth of human pancreatic cancer xenografts and induce apoptosis through the mitochondrial pathway. 1248 14