1. Marein, a novel natural product for restoring chemo-sensitivity to cancer cells through competitive inhibition of ABCG2 function.
- Author
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Li Y, Guo F, Wang W, Lv F, Zhang L, Zhu M, Yang S, Dong S, Zhou M, Li Z, Zhu Z, Yang JM, and Zhang Y
- Subjects
- Humans, Biological Products pharmacology, Biological Products chemistry, Cell Line, Tumor, HEK293 Cells, Antineoplastic Agents pharmacology, ATP Binding Cassette Transporter, Subfamily G, Member 2 metabolism, ATP Binding Cassette Transporter, Subfamily G, Member 2 antagonists & inhibitors, ATP Binding Cassette Transporter, Subfamily G, Member 2 genetics, Drug Resistance, Neoplasm drug effects, Drug Resistance, Neoplasm physiology, Neoplasm Proteins metabolism, Neoplasm Proteins antagonists & inhibitors, Neoplasm Proteins genetics, Chalcones therapeutic use
- 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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