Investigation of the apoptosis‐inducing effect of docetaxel by comprehensive LC–MS–based metabolomics and network pharmacology approaches

Abstract

Docetaxel is one of the clinical first‐line drugs and its combination with other chemotherapy agents for advanced or metastatic cancers has attracted widespread attention. Therefore, to promote the clinical application of docetaxel alone or in combination, a comprehensive investigation of the metabolic mechanism of docetaxel is of great importance. Here, we apply an integrative analysis of metabolomics and network pharmacology to elucidate the underlying mechanisms of docetaxel. After taking the intersection of the aforesaid two methods, five pathways including ABC (ATP‐binding cassette) transporters, central carbon metabolism in cancer, glycolysis and gluconeogenesis, cysteine and methionine metabolism, and arginine biosynthesis have been screened. Concerning the interaction network of these pathways and the anti‐apoptosis effect of docetaxel itself, the central carbon metabolism in cancer pathway was mainly focused on. This study may help delineate global landscapes of cellular protein–metabolite interactions, to provide molecular insights about their mechanisms of action as well as to promote their clinical applications.

Apoptosis, a Metabolic “Head-to-Head” between Tumor and T Cells: Implications for Immunotherapy

“…Nevertheless, docetaxel employs several different mechanisms to allow cancer cell survival [ 242 ]. Metabolomic studies have provided a chance to monitor its effects, as described by Wang et al [ 243 ]. Among the numerous significant pathways identified in treated cervical cancer cells that are deregulated by docetaxel, ABC transporters have proved the most statistically significant and strongly associated with chemoresistance [ 244 ].…”

“…From a metabolic perspective, central carbon metabolism is crucially interconnected to glycolysis/gluconeogenesis, cysteine, and methionine metabolism, as well as arginine biosynthesis. These pathways are under the control of RTKs-mediated MAPK signaling or the HER2-mediated PI3K–AKT–mTOR axis [ 243 ].…”

Docetaxel suppressed cell proliferation through Smad3/HIF-1α-mediated glycolysis in prostate cancer cells

“…Docetaxel, the first-line chemotherapeutic agent for advanced stage prostate cancer [ 14 ], is gradually gained widespread attention due to its novel function has been identified [ 15 , 16 ], However, the toxic side effects and drug resistance limited clinical success of Docetaxel. Early staged and localized PCa can be well controlled by prostatectomy or radiotherapy.…”