Laboratorio de Biología del Cáncer, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB-UNS-CONICET), Bahía Blanca, Argentina.
Laboratorio de Bioquímica de Lípidos, Departamento de Biología, Bioquímica y Farmacia (UNS), Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB-UNS-CONICET), Argentina, 8000, Bahía Blanca, CP, Argentina.
Sci Rep. 2023 Jun 21;13(1):10091. doi: 10.1038/s41598-023-35125-4.
Heme, an iron-containing prosthetic group found in many proteins, carries out diverse biological functions such as electron transfer, oxygen storage and enzymatic reactions. Hemin, the oxidised form of heme, is used to treat porphyria and also to activate heme-oxygenase (HO) which catalyses the rate-limiting step in heme degradation. Our group has previously demonstrated that hemin displays antitumor activity in breast cancer (BC). The aim of this work has been to study the effect of hemin on protein expression modifications in a BC cell line to gain insight into the molecular mechanisms of hemin antitumor activity. For this purpose, we carried out proteome analysis by Mass Spectrometry (MS) which showed that 1309 proteins were significantly increased in hemin-treated cells, including HO-1 and the proteases that regulate HO-1 function, and 921 proteins were significantly decreased. Furthermore, the MS-data analysis showed that hemin regulates the expression of heme- and iron-related proteins, adhesion and cytoskeletal proteins, cancer signal transduction proteins and enzymes involved in lipid metabolism. By biochemical and cellular studies, we further corroborated the most relevant in-silico results. Altogether, these results show the multiple physiological effects that hemin treatment displays in BC and demonstrate its potential as anticancer agent.
血红素是一种存在于许多蛋白质中的含铁辅基，具有多种生物学功能，如电子传递、氧气储存和酶反应。血红素是血红素的氧化形式，用于治疗卟啉症，并激活血红素加氧酶（HO），催化血红素降解的限速步骤。我们的研究小组先前证明，血红素在乳腺癌（BC）中具有抗肿瘤活性。这项工作的目的是研究血红素对 BC 细胞系中蛋白质表达修饰的影响，以深入了解血红素抗肿瘤活性的分子机制。为此，我们通过质谱（MS）进行了蛋白质组分析，结果表明血红素处理的细胞中 1309 种蛋白质的表达显著增加，包括 HO-1 和调节 HO-1 功能的蛋白酶，921 种蛋白质的表达显著降低。此外，MS 数据分析表明，血红素调节血红素和铁相关蛋白、黏附蛋白和细胞骨架蛋白、癌症信号转导蛋白以及参与脂质代谢的酶的表达。通过生化和细胞研究，我们进一步证实了最相关的计算机模拟结果。总之，这些结果表明血红素处理在 BC 中具有多种生理作用，并证明其作为抗癌剂的潜力。
