Proteomic study of breast cancer cell line after HO-1 modulation by hemin treatment

Abstract

Hemoxygenase-1 (HO-1) is a microsomal enzyme that catalyzes the degradation of the heme group and it can be translocated to multiple subcellular compartments. Our laboratory, among others, has shown that HO-1 regulates several processes related to cancer progression such as: proliferation, invasion migration, metastasis and the epithelial- mesenchymal transition. The aim of this work is to investigate the role of HO-1 in the proteome modulation in a breast cancer cell line. Protein extracts of LM3 cell line treated with hemin, a pharmacological HO-1 inducer (80 μM, 24 h), were obtained and studied by Western blot and Mass Spectrometry (MS). MS-data analysis showed 1,033 from 7,292 proteins were modulated after hemin treatment (ANOVA, p <0.05). We observed that 595 proteins were increased, including HO-1 and 353 proteins were decreased in the group treated with hemin respect to their controls. Hemin treatment in LM3 cells induce lipid metabolism, heme and iron related protein expression. By thin layer cromatography, we observed an increase fraction of phosphatidyl serine, phosphatidylinositol, phosphatidylethanolamine and triglycerides after hemin treatment in LM3 cells, confirming the role of HO-1 in lipids metabolism. In addition, hemin treatment decreases the ribosomal RNA biogenesis and cytoskeleton and microtubules related proteins. These results show the multiple physiological effects of HO-1 in a breast cancer cell line.