Metabolomics–Proteomics Combined Approach Identifies Differential Metabolism-Associated Molecular Events between Senescence and Apoptosis

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.