Integrative Omics Analysis Revealed Metabolic Intervention Combined with Metronomic Chemotherapy Selectively Kills Cancer Cells

Metronomic chemotherapy, a relatively new dosing paradigm for anti-cancer therapy, is an alternative to traditional chemotherapy that uses maximal tolerated dose (MTD). Although these two dosing regimens both lead to tumor cell death, how cell metabolism is differentially affected during apoptosis remains elusive. Herein, we employed metabolomics to monitor the metabolic profiles of MCF-7 cells in response to the two dosing regimens that mimic MTD and MN treatments using a model chemotherapeutic drug, Doxorubicin (Dox), and correlated the changes of metabolic genes examined by PCR array to integratively describe the reprogrammed metabolic patterns. We found glycolysis, amino acid and nucleotide synthesis-associated metabolic pathways were activated in response to the MN treatment, whereas these pathways were pronouncedly inhibited in response to the MTD treatment. Direct supplementation of key metabolites and pharmacological modulation of targeted metabolic enzymes can both regulate cell fates. Subsequent...