title: Metabolomics Analysis of Hormone-Responsive and Triple-Negative Breast Cancer Cell Responses to Paclitaxel Identify Key Metabolic Differences.
abstract: To date, no targeted therapies are available to treat triple negative breast cancer (TNBC), while other breast cancer subtypes are responsive to current therapeutic treatment. Metabolomics was conducted to reveal differences in two hormone receptor-negative TNBC cell lines and two hormone receptor-positive Luminal A cell lines. Studies were conducted in the presence and absence of paclitaxel (Taxol). TNBC cell lines had higher levels of amino acids, branched-chain amino acids, nucleotides, and nucleotide sugars and lower levels of proliferation-related metabolites like choline compared with Luminal A cell lines. In the presence of paclitaxel, each cell line showed unique metabolic responses, with some similarities by type. For example, in the Luminal A cell lines, levels of lactate and creatine decreased while certain choline metabolites and myo-inositol increased with paclitaxel. In the TNBC cell lines levels of glutamine, glutamate, and glutathione increased, whereas lysine, proline, and valine decreased in the presence of drug. Profiling secreted inflammatory cytokines in the conditioned media demonstrated a greater response to paclitaxel in the hormone-positive Luminal cells compared with a secretion profile that suggested greater drug resistance in the TNBC cells. The most significant differences distinguishing the cell types based on pathway enrichment analyses were related to amino acid, lipid and carbohydrate metabolism pathways, whereas several biological pathways were differentiated between the cell lines following treatment.
authors.affiliation: NIH Eastern Regional Comprehensive Metabolomics Resource Core, RTI International , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Delisha A
authors.initials: DA
authors.lastname: Stewart
authors.affiliation: David H. Murdock Research Institute , Kannapolis, North Carolina 28081, United States.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Winnike
authors.affiliation: NIH Eastern Regional Comprehensive Metabolomics Resource Core, RTI International , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Susan L
authors.initials: SL
authors.lastname: McRitchie
authors.affiliation: NIH Eastern Regional Comprehensive Metabolomics Resource Core, RTI International , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Clark
authors.affiliation: NIH Eastern Regional Comprehensive Metabolomics Resource Core, RTI International , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Wimal W
authors.initials: WW
authors.lastname: Pathmasiri
authors.affiliation: NIH Eastern Regional Comprehensive Metabolomics Resource Core, RTI International , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Sumner
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D050260:Carbohydrate Metabolism; D045744:Cell Line, Tumor; D005260:Female; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D050356:Lipid Metabolism; D053858:Metabolic Networks and Pathways; D008660:Metabolism / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods*; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D010634:Phenobarbital; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D006728:Hormones; D017239:Paclitaxel; D010634:Phenobarbital
keywords: Luminal A; cell lines; cytokines; health disparity; metabolomics; paclitaxel/Taxol; triple negative breast cancer (TNBC)