Frontiers in Pharmacology (Dec 2019)

Discovery of Novel Doxorubicin Metabolites in MCF7 Doxorubicin-Resistant Cells

  • Xu Wang,
  • Renjie Hui,
  • Yun Chen,
  • Wentao Wang,
  • Yujiao Chen,
  • Xiaohai Gong,
  • Jian Jin

DOI
https://doi.org/10.3389/fphar.2019.01434
Journal volume & issue
Vol. 10

Abstract

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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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