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:10.3389/fphar.2019.01434

Discovery of Novel Doxorubicin Metabolites in MCF7 Doxorubicin-Resistant Cells

Xu Wang (Co-first Author)
, Renjie Hui (Co-first Author)
, Yun Chen
, Wentao Wang
, Yujiao Chen
, Xiaohai Gong
, Jian Jin^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

21 Citations (Scopus)

42 Downloads (CityUHK Scholars)

Abstract

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. Copyright © 2019 Wang, Hui, Chen, Wang, Chen, Gong and Jin.

Original language	English
Article number	1434
Journal	Frontiers in Pharmacology
Volume	10
Online published	6 Dec 2019
DOIs	https://doi.org/10.3389/fphar.2019.01434
Publication status	Published - Dec 2019
Externally published	Yes

Bibliographical note

Funding

This study was supported by the National Natural Science Foundation of China (Grant Nos. 30772586 and 81361168001) and The Clinical Science and Technology Projects (Grant No. BL2014019).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

drug resistant
doxorubicin
intracellular drug metabolism
LC-MS/MS
breast cancer

Publisher's Copyright Statement

This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

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10.3389/fphar.2019.01434

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title = "Discovery of Novel Doxorubicin Metabolites in MCF7 Doxorubicin-Resistant Cells",

abstract = "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. Copyright {\textcopyright} 2019 Wang, Hui, Chen, Wang, Chen, Gong and Jin.",

keywords = "drug resistant, doxorubicin, intracellular drug metabolism, LC-MS/MS, breast cancer",

author = "Xu Wang and Renjie Hui and Yun Chen and Wentao Wang and Yujiao Chen and Xiaohai Gong and Jian Jin",

note = "Copyright {\textcopyright} 2019 Wang, Hui, Chen, Wang, Chen, Gong and Jin.",

year = "2019",

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doi = "10.3389/fphar.2019.01434",

language = "English",

volume = "10",

journal = "Frontiers in Pharmacology",

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TY - JOUR

T1 - Discovery of Novel Doxorubicin Metabolites in MCF7 Doxorubicin-Resistant Cells

AU - Wang, Xu

AU - Hui, Renjie

AU - Chen, Yun

AU - Wang, Wentao

AU - Chen, Yujiao

AU - Gong, Xiaohai

AU - Jin, Jian

PY - 2019/12

Y1 - 2019/12

N2 - 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. Copyright © 2019 Wang, Hui, Chen, Wang, Chen, Gong and Jin.

AB - 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. Copyright © 2019 Wang, Hui, Chen, Wang, Chen, Gong and Jin.

KW - drug resistant

KW - doxorubicin

KW - intracellular drug metabolism

KW - LC-MS/MS

KW - breast cancer

UR - https://www.scopus.com/pages/publications/85076958719

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85076958719&origin=recordpage

U2 - 10.3389/fphar.2019.01434

DO - 10.3389/fphar.2019.01434

M3 - RGC 21 - Publication in refereed journal

C2 - 31866863

SN - 1663-9812

VL - 10

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

M1 - 1434

ER -

Discovery of Novel Doxorubicin Metabolites in MCF7 Doxorubicin-Resistant Cells

Abstract

Bibliographical note

Funding

UN SDGs

Research Keywords

Publisher's Copyright Statement

Access Output

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