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

被引:12
作者
Wu, Chung-Pu [1 ,2 ]
Li, Yan-Qing [1 ]
Hung, Tai-Ho [2 ,3 ]
Chang, Yu-Tzu [4 ]
Huang, Yang-Hui [1 ,4 ]
Wu, Yu-Shan [5 ]
机构
[1] Chang Gung Univ, Grad Inst Biomed Sci, Taoyuan 33302, Taiwan
[2] Taipei Chang Gung Mem Hosp, Dept Obstet & Gynecol, Taipei 33305, Taiwan
[3] Chang Gung Univ, Coll Med, Dept Chinese Med, Taoyuan 33302, Taiwan
[4] Chang Gung Univ, Dept Physiol & Pharmacol, Taoyuan 33302, Taiwan
[5] Tunghai Univ, Dept Chem, Taichung 40704, Taiwan
来源
JOURNAL OF NATURAL PRODUCTS | 2021年 / 84卷 / 09期
关键词
BINDING CASSETTE TRANSPORTER; TYROSINE KINASE INHIBITORS; G INDUCES APOPTOSIS; ANTIBACTERIAL ACTIVITY; ACQUIRED-RESISTANCE; SOPHORA-FLAVESCENS; LAVANDULYL FLAVANONES; ABCG2; POLYMORPHISMS; GENE-EXPRESSION; PHASE-II;
D O I
10.1021/acs.jnatprod.1c00584
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
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. Sophora-flavanone G (SFG), a phytoncide isolated from the plant species Sophora 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.
引用
收藏
页码:2544 / 2553
页数:10
相关论文
共 96 条
  • [1] Biochemical, cellular, and pharmacological aspects of the multidrug transporter
    Ambudkar, SV
    Dey, S
    Hrycyna, CA
    Ramachandra, M
    Pastan, I
    Gottesman, MM
    [J]. ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1999, 39 : 361 - 398
  • [2] Systemic Therapy for Locally Advanced and Metastatic Non-Small Cell Lung Cancer A Review
    Arbour, Kathryn C.
    Riely, Gregory J.
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2019, 322 (08): : 764 - 774
  • [3] The FLT3 Inhibitor Quizartinib Inhibits ABCG2 at Pharmacologically Relevant Concentrations, with Implications for Both Chemosensitization and Adverse Drug Interactions
    Bhullar, Jasjeet
    Natarajan, Karthika
    Shukla, Suneet
    Mathias, Trevor J.
    Sadowska, Mariola
    Ambudkar, Suresh V.
    Baer, Maria R.
    [J]. PLOS ONE, 2013, 8 (08):
  • [4] Interaction of hesperetin glucuronide conjugates with human BCRP, MRP2 and MRP3 as detected in membrane vesicles of overexpressing baculovirus-infected Sf9 cells
    Brand, Walter
    Oosterhuis, Berend
    Krajcsi, Peter
    Barron, Denis
    Dionisi, Fabiola
    van Bladeren, Peter J.
    Rietjens, Ivonne M. C. M.
    Williamson, Gary
    [J]. BIOPHARMACEUTICS & DRUG DISPOSITION, 2011, 32 (09) : 530 - 535
  • [5] The effect of co-administered flavonoids on the metabolism of hesperetin and the disposition of its metabolites in Caco-2 cell monolayers
    Brand, Walter
    Padilla, Beatriz
    van Bladeren, Peter J.
    Williamson, Gary
    Rietjens, Ivonne M. C. M.
    [J]. MOLECULAR NUTRITION & FOOD RESEARCH, 2010, 54 (06) : 851 - 860
  • [6] Brangi M, 1999, CANCER RES, V59, P5938
  • [7] Cha JD, 2007, J MICROBIOL BIOTECHN, V17, P858
  • [8] Antibacterial Activity of sophoraflavanone G Isolated from the Roots of Sophora flavescens against Methicillin-Resistant Staphylococcus aureus
    Cha, Jeong-Dan
    Moon, Sang-Eun
    Kim, Ji-Young
    Jung, Eun-Kyung
    Lee, Young-Soo
    [J]. PHYTOTHERAPY RESEARCH, 2009, 23 (09) : 1326 - 1331
  • [9] A Novel Flavonoid Kushenol Z from Sophora flavescens Mediates mTOR Pathway by Inhibiting Phosphodiesterase and Akt Activity to Induce Apoptosis in Non-Small-Cell Lung Cancer Cells
    Chen, Hao
    Yang, Jie
    Hao, Ji
    Lv, Yibing
    Chen, Lu
    Lin, Qinxiong
    Yuan, Jingquan
    Yang, Xinzhou
    [J]. MOLECULES, 2019, 24 (24):
  • [10] Impact of ABCG2 polymorphisms on the clinical outcome of TKIs therapy in Chinese advanced non-small-cell lung cancer patients
    Chen, Xueqin
    Chen, Dadong
    Yang, Shaoyu
    Ma, Ruobing
    Pan, Yuelong
    Li, Xin
    Ma, Shenglin
    [J]. CANCER CELL INTERNATIONAL, 2015, 15 : 1