GC‐MS based comparative metabolomic analysis of MCF7 and MDA‐MB‐231 cancer cells treated with Tamoxifen and/or Taxol

Abstract

Metabolomics of cancer cells is a powerful tool to understand the development, progression and treatment outcome of different types of cancer. Therefore, a highly sensitive, selective and reproducible platform that provides deep information about modifications of metabolism of cancer cells undergoing chemotherapy is required. In the present study, Tamoxifen (5μM) and/or Taxol (1μM) were added to MCF7 and MDA‐MB‐231 cancer cells to investigate the effect of these drugs on the metabolism of the treated cells. In the breast cancer cells (MCF7), of the 68 metabolites identified, 20 were differentially abundant in treated cells with treatment (p< 0.01). Subsequent enriched metabolic pathway analysis (MetaboAnalyst) revealed that tamoxifen had a significant impact in the steroid biosynthesis. Specifically, there was a 32‐fold increase of Lathosterol with tamoxifen, while Zymosterol had a 2.7‐fold decrease with tamoxifen and Desmosterol has decreased by 27‐fold under treatment with both drugs. Additionally, treatment with both drugs had an impact on amino acid pathways (Glycine, Phenylalanine, Threonine, Valine). On the other hand, 59 metabolites have been identified in MDA‐MB‐231 cells. Fourteen of them were differentially abundant in treated cells (p< 0.01). Unlike the MCF7, drug treatment had no effect in the aa pathway in MDA‐MB‐231 cells and seemed to mainly impact sugar metabolism. For example, treatment with tamoxifen lowered the levels of sugars like L‐Rhamnose, Glycerol, while Xylose decreased only upon treatment with combination of the two drugs. Our data showed that a set of metabolites was affected by the presence of either of the drugs, however there was a number of metabolites that responded to a specific drug treatment. This result suggests that a combination of tamoxifen and taxol may be considered as an alternative therapy against cancer cells.