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Updated: Mar 3, 2026
Measurement of Protein Turnover Rates in Senescent and Non-Dividing Cultured Cells with Metabolic Labeling and Mass Spectrometry
Published on: April 6, 2022
Metabolomics-Proteomics Combined Approach Identifies Differential Metabolism-Associated Molecular Events between
Mengqiu Wu1, Hui Ye1, Chang Shao1
1Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines and ‡School of Pharmacy, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 210009, China.
Abstract:
Apoptosis and senescence are two types of cell fates in response to chemotherapy. Besides canonical pathways that mediate cell fates, cancer cell metabolism has been revealed as a crucial factor affecting cell fate decisions and thus represents a new target for antitumor therapy. Therefore, a comprehensive description of metabolic pathways underlying cell senescence and apoptosis in response to chemotherapy is highly demanded for therapeutic exploitation of both processes. Herein we employed a metabolomics-proteomics combined approach to identify metabolism-associated molecular events that mediate cellular responses to senescence and apoptosis using doxorubicin-treated human breast cancer cells MCF7 as models. Such biomics approach revealed that tricarboxylic acid cycle, pentose phosphate pathway, and nucleotide synthesis pathways were significantly upregulated in the senescent model, whereas fatty acid synthesis was reduced. In apoptotic cells, an overall reduced activity of major metabolic pathways was observed except for the arginine and proline pathway. Combinatorially, these data show the utility of biomics in exploring biochemical mechanism-based differences between apoptosis and senescence and reveal an unprecedented finding of the metabolic events that were induced for survival by facilitating ROS elimination and DNA damage repair in senescent cells, while they were downregulated in apoptotic cells when DNA damage was irreparable.
Insights
Cancer cell metabolism significantly impacts chemotherapy outcomes, influencing apoptosis and senescence. This study reveals distinct metabolic shifts in senescent cells promoting survival via DNA repair and ROS elimination, unlike apoptotic cells.
Area of Science:
- Cancer Biology
- Metabolic Pathways
- Cellular Senescence and Apoptosis
Background:
- Cellular fate decisions (apoptosis and senescence) are critical responses to chemotherapy.
- Cancer cell metabolism plays a crucial role in mediating these cell fate decisions.
- Targeting metabolic pathways offers a novel therapeutic strategy for cancer treatment.
Purpose of the Study:
- To comprehensively describe metabolic pathways involved in chemotherapy-induced cell senescence and apoptosis.
- To identify metabolism-associated molecular events mediating cellular responses to senescence and apoptosis.
- To explore biochemical mechanism-based differences between apoptosis and senescence using a combined biomics approach.
Main Methods:
- Employed a combined metabolomics-proteomics approach.
- Utilized doxorubicin-treated human breast cancer cells (MCF7) as a model system.
- Analyzed metabolic pathway activity in senescent versus apoptotic cellular models.
Main Results:
- Senescent cells showed significant upregulation of the tricarboxylic acid cycle, pentose phosphate pathway, and nucleotide synthesis, with reduced fatty acid synthesis.
- Apoptotic cells exhibited overall reduced metabolic pathway activity, with the exception of the arginine and proline pathway.
- Senescent cells displayed metabolic adaptations for survival, including reactive oxygen species (ROS) elimination and DNA damage repair.
Conclusions:
- Metabolomics and proteomics are valuable tools for elucidating biochemical differences between apoptosis and senescence.
- Distinct metabolic reprogramming underlies senescent versus apoptotic cell fates in response to chemotherapy.
- Senescent cells activate specific metabolic pathways to survive chemotherapy by managing DNA damage and oxidative stress.
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