Untargeted Metabolomics of Breast Cancer Cells MCF-7 and SkBr3 Treated With Tamoxifen/Trastuzumab

Abstract

Background/Aim: Trastuzumab and tamoxifen are two of the most widely prescribed anti-cancer drugs for breast cancer (BC). To date, few studies have explored the impact of anticancer drugs on metabolic pathways in BC. Metabolomics is an emerging technology that can identify new biomarkers for tracking therapy response and novel therapeutic targets. Materials and Methods: We employed ultra-high-performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) to investigate changes in MCF-7 and SkBr3 cell lines treated with either tamoxifen, trastuzumab or a combination of both. The Bruker Human Metabolome Database (HMDB) metabolite library was used to match spectra and the MetaboScape software to assign each feature with a putative metabolite name or molecular formula for metabolite annotation. Results: A total of 98 metabolites were found to significantly differ in abundance in MCF-7 and SkBr3 treated cells. Moreover, the metabolic profile of the combination medication is similar to that of tamoxifen alone, according to functional enrichment analysis. Conclusion: Tamoxifen/trastuzumab treatment had a significant effect on pathways essential for the control of energy-production, which have previously been linked to cancer progression, and aggressivenessCancer is considered the second leading cause of death after heart disease with the number of cases estimated to grow to over 13.1 million by 2030 (1). Worldwide, breast cancer (BC) is the second leading cause of cancer-related death, after lung cancer, among women (2-5). This cancer type is recognized as a heterogeneous and multifaceted disease with a varied range of pathological, clinical, and molecular characteristics. BC is hormone-responsive and classified into three subtypes based on specific estrogen (E), progesterone (P), and human epidermal growth factor molecular biomarkers. The main hormones involved in the regulation of tumor growth or regression and cellular function are estrogen and progesterone. After malignant transformation, because the mammary glands contain unique receptor sites, the cells may maintain all or some of the normal complement of receptor sites (6-9). With respect to the retained receptor sites, breast tumors are classified as one of the estrogen-or progesterone-positive or -negative receptor (ER-/PRpositive/-negative) subtypes. Experimental breast tumor models demonstrate evidence of PR estrogen regulation, indicating that PR is present in approximately 59% of ERpositive metastatic tumors (10,11). Clinical studies have shown that women with hormone receptor-positive tumors have successfully survived therapy with adjuvant hormone and/or chemotherapy regimens (12, 13). Human epidermal growth factor receptor (HER2) is a third molecular target that belongs to the transmembrane receptor tyrosine kinase family. It plays an essential role in the mediation of growth and progression of breast cancer cells (14). Worldwide, approximately 20% of BC overexpress the HER2 receptor 79 This article is freely accessible onli...

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