Effect of 5-lipoxygenase protein expression in malignant breast cancer cells and mechanisms involved in tumor suppression

Breast cancer remains a major threat to women's health worldwide, and exploring novel therapeutic targets is urgently needed. Inhibiting 5-lipoxygenase (5-LOX) showed promising potential in treating various malignancies. However, 5-LOX effects on breast cancer progression are largely unknown. Breast cancer cell lines (MCF-7 and MDA-MB-231) and nonmalignant breast epithelial cells (MCF-10A) were used in this study. The expression of 5-LOX was quantified by RT-qPCR and Western blot analysis. 5-LOX was upregulated by pCDNA3.1(+)-5-LOX transfection and inhibited using zileuton. The influence of 5-LOX modulation on cell apoptosis, invasion, and colony formation was determined using flow cytometry, Transwell invasion assay, and colony formation assay, respectively. Results demonstrated that 5-LOX mRNA and protein expression levels were significantly higher in breast cancer cells compared with nonmalignant breast epithelial cells. Transfection with pCDNA3.1(+)-5-LOX significantly upregulated 5-LOX expression, while zileuton, an anti-inflammatory leukotriene inhibitor of 5-LOX, treatment (400 μmol/L) markedly downregulated 5-LOX mRNA and protein levels. Treatment with zileuton significantly induced apoptosis in MCF-7 and inhibited in MDA-MB-231 cell invasion. Further, zileuton suppressed colony formation in both breast cancer cell lines. Data suggest that 5-LOX may serve as a potential therapeutic target for breast cancer, and zileuton warrants further investigation as a candidate anti-cancer agent.