Related Experiment Video
Updated: Mar 17, 2026
Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
Published on: May 14, 2018
Metabolomics Analysis of Hormone-Responsive and Triple-Negative Breast Cancer Cell Responses to Paclitaxel Identify
Delisha A Stewart1, Jason H Winnike2, Susan L McRitchie1
1NIH Eastern Regional Comprehensive Metabolomics Resource Core, RTI International , Research Triangle Park, North Carolina 27709, United States.
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.
Insights
Metabolomics reveals distinct metabolic profiles between triple-negative breast cancer (TNBC) and hormone-positive breast cancer cells. TNBC cells exhibit drug resistance, suggesting new therapeutic targets for this aggressive cancer subtype.
Area of Science:
- Biochemistry
- Oncology
- Metabolomics
Background:
- Triple-negative breast cancer (TNBC) lacks targeted therapies, unlike other breast cancer subtypes.
- Metabolic differences between TNBC and hormone-positive breast cancer remain underexplored.
Purpose of the Study:
- To investigate metabolic differences between TNBC and Luminal A breast cancer cell lines.
- To assess metabolic responses to paclitaxel in these cell lines.
- To identify potential therapeutic targets for TNBC.
Main Methods:
- Metabolomic profiling of two TNBC and two Luminal A cell lines.
- Treatment with paclitaxel (Taxol) in vitro.
- Analysis of secreted inflammatory cytokines.
- Pathway enrichment analysis.
Main Results:
- TNBC cells showed higher amino acids, branched-chain amino acids, nucleotides, and nucleotide sugars; lower choline compared to Luminal A cells.
- Paclitaxel induced unique metabolic shifts in each cell type, with Luminal A cells showing decreased lactate/creatine and increased choline metabolites/myo-inositol.
- TNBC cells exhibited increased glutamine, glutamate, glutathione, and decreased lysine, proline, valine upon paclitaxel treatment.
- Luminal A cells demonstrated a greater inflammatory cytokine response to paclitaxel, suggesting higher drug sensitivity compared to TNBC cells, which indicated drug resistance.
- Pathway analysis highlighted significant differences in amino acid, lipid, and carbohydrate metabolism between cell types, and further differentiation after treatment.
Conclusions:
- Distinct metabolic profiles differentiate TNBC from Luminal A breast cancer cells.
- TNBC cells display inherent resistance to paclitaxel, evidenced by metabolic and inflammatory responses.
- Metabolic pathways, particularly amino acid, lipid, and carbohydrate metabolism, represent potential targets for novel TNBC therapies.
