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 aggressiveness.

Keywords: MCF-7; SkBr3; UHPLC-trapped ion TIMS-QTOF; Untargeted metabolomics; breast cancer cells; tamoxifen; trastuzumab.