Sophoraflavanone G Resensitizes ABCG2-Overexpressing Multidrug-Resistant Non-Small-Cell Lung Cancer Cells to Chemotherapeutic Drugs

Chung Pu Wu*, Yan Qing Li, Tai Ho Hung, Yu Tzu Chang, Yang Hui Huang, Yu Shan Wu

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

9 Scopus citations

Abstract

Elevated expression of the ATP-binding cassette (ABC) drug transporter ABCG2 in cancer cells contributes to the development of the multidrug resistance phenotype in patients with advanced non-small-cell lung cancer (NSCLC). Due to the lack of U.S. Food and Drug Administration (FDA)-approved synthetic inhibitors of ABCG2, significant efforts have been invested in discovering bioactive compounds of plant origin that are capable of reversing ABCG2-mediated multidrug resistance in cancer cells. Sophoraflavanone G (SFG), a phytoncide isolated from the plant speciesSophora flavescens, is known to possess a wide spectrum of pharmacological activities, including antibacterial, anti-inflammatory, antimalarial, and antiproliferative effects. In the present study, the chemosensitizing effect of SFG in ABCG2-overexpressing NSCLC cells was investigated. Experimental results demonstrate that at subtoxic concentrations SFG significantly reversed ABCG2-mediated multidrug resistance in a concentration-dependent manner. Additional biochemical data and in silico docking analysis of SFG to the inward-open conformation of human ABCG2 indicate that SFG inhibited the drug transport function of ABCG2 by interacting with residues within the transmembrane substrate-binding pocket of ABCG2. Collectively, these findings provide evidence that SFG has the potential to be further tested as an effective inhibitor of ABCG2 to improve the efficacy of therapeutic drugs in patients with advanced NSCLC.

Original languageEnglish
Pages (from-to)2544-2553
Number of pages10
JournalJournal of Natural Products
Volume84
Issue number9
DOIs
StatePublished - 24 09 2021

Bibliographical note

Publisher Copyright:
© 2021 American Chemical Society and American Society of Pharmacognosy

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