Marein, a novel natural product for restoring chemo-sensitivity to cancer cells through competitive inhibition of ABCG2 function

Yixuan Li; Fanfan Guo; Wenjing Wang; Fang Lin Lv; Lu Zhang; Mingxian Zhu; Shumin Yang; Shunli Dong; Mingxuan Zhou; Zhenyun Li; Zengyan Zhu; Jin Ming Yang; Yi Zhang

doi:10.1016/j.bcp.2024.116219

Marein, a novel natural product for restoring chemo-sensitivity to cancer cells through competitive inhibition of ABCG2 function

Yixuan Li, Fanfan Guo, Wenjing Wang, Fang Lin Lv, Lu Zhang, Mingxian Zhu, Shumin Yang, Shunli Dong, Mingxuan Zhou, Zhenyun Li, Zengyan Zhu, Jin Ming Yang, Yi Zhang

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

The pivotal roles of ATP-binding cassette (ABC) transporters in drug resistance have been widely appreciated. Here we report that marein, a natural product from Coreopsis tinctoria Nutt, is a potent chemo-sensitizer in drug resistant cancer cells overexpressing ABCG2 transporter. We demonstrate that marein can competitively inhibit efflux activity of ABCG2 protein and increase the intracellular accumulation of the chemotherapeutic drugs that belong to substrate of this transporter. We further show that marein can bind to the conserved amino acid residue F439 of ABCG2, a critical site for drug-substrate interaction. Moreover, marein can significantly sensitize the ABCG2-expressing tumor cells to chemotherapeutic drugs such as topotecan, mitoxantrone, and olaparib. This study reveals a novel role and mechanism of marein in modulating drug resistance, and may have important implications in treatment of cancers that are resistant to chemotherapeutic drugs that belong to the substrates of ABCG2 transporters.

Original language	English
Article number	116219
Journal	Biochemical Pharmacology
Volume	228
DOIs	https://doi.org/10.1016/j.bcp.2024.116219
State	Published - Oct 2024

Bibliographical note

Publisher Copyright:
© 2024 Elsevier Inc.

Funding

This work was supported by grants from National Natural Sciences Foundation of China to Yi Zhang (81773749, 81973352, 82273944), sponsored by the Qing Lan Project (to Yi Zhang) and by a project funded by the Priority Academic Program Development of the Jiangsu Higher Education Institutes (PAPD), supported by Beijing Medical Award Foundation\uFF08YXJL-2023-0227-0107\uFF09to Zengyan Zhu and Aosaikang Hospital Pharmacy Foundation of Jiangsu Province Pharmaceutical Association (A202121) to Wenjing Wang.

Funders	Funder number
Qinglan Project of Jiangsu Province of China
Priority Academic Program Development of Jiangsu Higher Education Institutions
Aosaikang Hospital Pharmacy Foundation of Jiangsu Province Pharmaceutical Association	A202121
Beijing Medical Award Foundation	YXJL-2023-0227-0107
National Natural Science Foundation of China (NSFC)	81973352, 81773749, 82273944
National Natural Science Foundation of China (NSFC)

Keywords

ABCG2
ATP-binding cassette transporter
Chemotherapy
Drug resistance
Marein

ASJC Scopus subject areas

Biochemistry
Pharmacology

UN SDGs

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

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10.1016/j.bcp.2024.116219

Cite this

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title = "Marein, a novel natural product for restoring chemo-sensitivity to cancer cells through competitive inhibition of ABCG2 function",

abstract = "The pivotal roles of ATP-binding cassette (ABC) transporters in drug resistance have been widely appreciated. Here we report that marein, a natural product from Coreopsis tinctoria Nutt, is a potent chemo-sensitizer in drug resistant cancer cells overexpressing ABCG2 transporter. We demonstrate that marein can competitively inhibit efflux activity of ABCG2 protein and increase the intracellular accumulation of the chemotherapeutic drugs that belong to substrate of this transporter. We further show that marein can bind to the conserved amino acid residue F439 of ABCG2, a critical site for drug-substrate interaction. Moreover, marein can significantly sensitize the ABCG2-expressing tumor cells to chemotherapeutic drugs such as topotecan, mitoxantrone, and olaparib. This study reveals a novel role and mechanism of marein in modulating drug resistance, and may have important implications in treatment of cancers that are resistant to chemotherapeutic drugs that belong to the substrates of ABCG2 transporters.",

keywords = "ABCG2, ATP-binding cassette transporter, Chemotherapy, Drug resistance, Marein",

author = "Yixuan Li and Fanfan Guo and Wenjing Wang and Lv, {Fang Lin} and Lu Zhang and Mingxian Zhu and Shumin Yang and Shunli Dong and Mingxuan Zhou and Zhenyun Li and Zengyan Zhu and Yang, {Jin Ming} and Yi Zhang",

note = "Publisher Copyright: {\textcopyright} 2024 Elsevier Inc.",

year = "2024",

month = oct,

doi = "10.1016/j.bcp.2024.116219",

language = "English",

volume = "228",

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AU - Li, Yixuan

AU - Guo, Fanfan

AU - Wang, Wenjing

AU - Lv, Fang Lin

AU - Zhang, Lu

AU - Zhu, Mingxian

AU - Yang, Shumin

AU - Dong, Shunli

AU - Zhou, Mingxuan

AU - Li, Zhenyun

AU - Zhu, Zengyan

AU - Yang, Jin Ming

AU - Zhang, Yi

PY - 2024/10

Y1 - 2024/10

N2 - The pivotal roles of ATP-binding cassette (ABC) transporters in drug resistance have been widely appreciated. Here we report that marein, a natural product from Coreopsis tinctoria Nutt, is a potent chemo-sensitizer in drug resistant cancer cells overexpressing ABCG2 transporter. We demonstrate that marein can competitively inhibit efflux activity of ABCG2 protein and increase the intracellular accumulation of the chemotherapeutic drugs that belong to substrate of this transporter. We further show that marein can bind to the conserved amino acid residue F439 of ABCG2, a critical site for drug-substrate interaction. Moreover, marein can significantly sensitize the ABCG2-expressing tumor cells to chemotherapeutic drugs such as topotecan, mitoxantrone, and olaparib. This study reveals a novel role and mechanism of marein in modulating drug resistance, and may have important implications in treatment of cancers that are resistant to chemotherapeutic drugs that belong to the substrates of ABCG2 transporters.

AB - The pivotal roles of ATP-binding cassette (ABC) transporters in drug resistance have been widely appreciated. Here we report that marein, a natural product from Coreopsis tinctoria Nutt, is a potent chemo-sensitizer in drug resistant cancer cells overexpressing ABCG2 transporter. We demonstrate that marein can competitively inhibit efflux activity of ABCG2 protein and increase the intracellular accumulation of the chemotherapeutic drugs that belong to substrate of this transporter. We further show that marein can bind to the conserved amino acid residue F439 of ABCG2, a critical site for drug-substrate interaction. Moreover, marein can significantly sensitize the ABCG2-expressing tumor cells to chemotherapeutic drugs such as topotecan, mitoxantrone, and olaparib. This study reveals a novel role and mechanism of marein in modulating drug resistance, and may have important implications in treatment of cancers that are resistant to chemotherapeutic drugs that belong to the substrates of ABCG2 transporters.

KW - ABCG2

KW - ATP-binding cassette transporter

KW - Chemotherapy

KW - Drug resistance

KW - Marein

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SN - 0006-2952

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JO - Biochemical Pharmacology

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ER -

Marein, a novel natural product for restoring chemo-sensitivity to cancer cells through competitive inhibition of ABCG2 function

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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