Why the study?
Doxorubicin is metabolized in vivo to metabolites associated with cardiotoxicity, and researchers hypothesized that metabolic processes are also present in tumor cells.
Drug-resistant breast cancer cells metabolize doxorubicin into three novel metabolites not found in wild-type cells, indicating a unique intracellular metabolism mechanism.
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Should not change DOX use in resistant tumors; leaves open metabolite roles in resistance and cardiotoxicity.
Doxorubicin (DOX) is metabolized to a variety of metabolites in vivo , which has been shown to be associated with cardiotoxicity. We speculate that metabolic processes are also present in tumor cells. A LC-MS/MS method was developed to detect intracellular metabolites. Drug resistant tumor cells with high drug stress tolerance and metabolically active are suitable as materials for this study. Our results show difference in drug metabolites between the wild-type and drug-resistant cells. Three novel doxorubicin metabolites were discovered after the LC-MS/MS analysis. All these metabolites and their profiles of metabolites are totally different from that in liver or kidney in vivo . Our results suggest that tumor cells and drug-resistant tumor cells have a unique drug metabolism pathway for doxorubicin.
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Wang et al. (2019) studied this question.
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