Imperatorin Restores Chemosensitivity of Multidrug-Resistant Cancer Cells by Antagonizing ABCG2-Mediated Drug Transport

被引:3
作者
Wu, Chung-Pu [1 ,2 ,3 ]
Murakami, Megumi [4 ]
Li, Yen-Ching [1 ]
Huang, Yang-Hui [1 ]
Chang, Yu-Tzu [1 ]
Hung, Tai-Ho [3 ,5 ,6 ]
Wu, Yu-Shan [7 ]
Ambudkar, Suresh V. [4 ]
机构
[1] Chang Gung Univ, Grad Inst Biomed Sci, Coll Med, Taoyuan 33302, Taiwan
[2] Chang Gung Univ, Coll Med, Dept Physiol & Pharmacol, Taoyuan 33302, Taiwan
[3] Taipei Chang Gung Mem Hosp, Dept Obstet & Gynecol, Taipei 10507, Taiwan
[4] NCI, Lab Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[5] Chang Gung Univ, Coll Med, Dept Med, Taoyuan 33302, Taiwan
[6] Keelung Chang Gung Mem Hosp, Dept Obstet & Gynecol, Keelung 20401, Taiwan
[7] Tunghai Univ, Dept Chem, Taichung 40704, Taiwan
关键词
ATP-binding cassette transporter; multidrug resistance; natural products; ABCG2; imperatorin; FUNCTIONAL-CHARACTERIZATION; KINASE INHIBITORS; NATURAL-PRODUCTS; GENE-EXPRESSION; IN-VITRO; ABCG2; PROTEIN; OVEREXPRESSION; APOPTOSIS; INDUCTION;
D O I
10.3390/ph16111595
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The high expression of the ATP-binding cassette (ABC) drug transporter ABCG2 in cancer cells contributes to the emergence of multidrug resistance (MDR) in individuals afflicted with either solid tumors or blood cancers. MDR poses a major impediment in the realm of clinical cancer chemotherapy. Recently, substantial endeavors have been dedicated to identifying bioactive compounds isolated from nature capable of counteracting ABCG2-mediated MDR in cancer cells. Imperatorin, a natural coumarin derivative renowned for its diverse pharmacological properties, has not previously been explored for its impact on cancer drug resistance. This study investigates the chemosensitizing potential of imperatorin in ABCG2-overexpressing cancer cells. Experimental results reveal that at sub-toxic concentrations, imperatorin significantly antagonizes the activity of ABCG2 and reverses ABCG2-mediated MDR in a concentration-dependent manner. Furthermore, biochemical data and in silico analysis of imperatorin docking to the inward-open conformation of human ABCG2 indicate that imperatorin directly interacts with multiple residues situated within the transmembrane substrate-binding pocket of ABCG2. Taken together, these results furnish substantiation that imperatorin holds promise for further evaluation as a potent inhibitor of ABCG2, warranting exploration in combination drug therapy to enhance the effectiveness of therapeutic agents for patients afflicted with tumors that exhibit high levels of ABCG2.
引用
收藏
页数:20
相关论文
共 50 条
  • [31] Ribophorin II potentiates P-glycoprotein- and ABCG2-mediated multidrug resistance via activating ERK pathway in gastric cancer
    Zhang, Hongzhi
    Jiang, Huijuan
    Zhang, Huixiang
    Liu, Juncai
    Hu, Xigang
    Chen, Lei
    INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2019, 128 : 574 - 582
  • [32] Sophoraflavanone G Resensitizes ABCG2-Overexpressing Multidrug-Resistant Non-Small-Cell Lung Cancer Cells to Chemotherapeutic Drugs
    Wu, Chung-Pu
    Li, Yan-Qing
    Hung, Tai-Ho
    Chang, Yu-Tzu
    Huang, Yang-Hui
    Wu, Yu-Shan
    JOURNAL OF NATURAL PRODUCTS, 2021, 84 (09): : 2544 - 2553
  • [33] Inhibition of drug transport by genistein in multidrug-resistant cells expressing P-glycoprotein
    Castro, AF
    Altenberg, GA
    BIOCHEMICAL PHARMACOLOGY, 1997, 53 (01) : 89 - 93
  • [34] Perspectives on drug repurposing to overcome cancer multidrug resistance mediated by ABCB1 and ABCG2
    Wu, Chung-Pu
    Hsiao, Sung-Han
    Wu, Yu-Shan
    DRUG RESISTANCE UPDATES, 2023, 71
  • [35] Functionalized Mesoporous Silica Nanoparticles for Drug-Delivery to Multidrug-Resistant Cancer Cells
    Igaz, Nora
    Belteky, Peter
    Kovacs, David
    Papp, Csaba
    Ronavari, Andrea
    Szabo, Diana
    Gacser, Attila
    Konya, Zoltan
    Kiricsi, Monika
    INTERNATIONAL JOURNAL OF NANOMEDICINE, 2022, 17 : 3079 - 3096
  • [36] Avapritinib: A Selective Inhibitor of KIT and PDGFRα that Reverses ABCB1 and ABCG2-Mediated Multidrug Resistance in Cancer Cell Lines
    Wu, Chung-Pu
    Lusvarghi, Sabrina
    Wang, Jyun-Cheng
    Hsiao, Sung-Han
    Huang, Yang-Hui
    Hung, Tai-Ho
    Ambudkar, Suresh V.
    MOLECULAR PHARMACEUTICS, 2019, 16 (07) : 3040 - 3052
  • [37] Pyrimido[1",2":1,5]pyrazolo[3,4-b]quinolines: Novel compounds that reverse ABCG2-mediated resistance in cancer cells
    Karthikeyan, Chandrabose
    Malla, Ritu
    Ashby, Charles R., Jr.
    Amawi, Haneen
    Abbott, Kodye L.
    Moore, Joshua
    Chen, Joel
    Balch, Curt
    Lee, Crystal
    Flannery, Patrick C.
    Trivedi, Piyush
    Faridi, Jesika S.
    Pondugula, Satyanarayana R.
    Tiwari, Amit K.
    CANCER LETTERS, 2016, 376 (01) : 118 - 126
  • [38] Gibberellin derivative GA-13315 sensitizes multidrug-resistant cancer cells by antagonizing ABCB1 while agonizes ABCC1
    Mo, Jiao
    Kang, Min
    Ye, Jun-Xian
    Chen, Jing-Bo
    Zhang, Hong-bin
    Qing, Chen
    CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2016, 78 (01) : 51 - 61
  • [39] Targeting the ABCG2-overexpressing multidrug resistant (MDR) cancer cells by PPARγ agonists
    To, Kenneth K. W.
    Tomlinson, Brian
    BRITISH JOURNAL OF PHARMACOLOGY, 2013, 170 (05) : 1137 - 1151
  • [40] Differential effects of calcium antagonists on ABCG2/BCRP-mediated drug resistance and transport in SN-38-resistant HeLa cells
    Takara, Kohji
    Matsubara, Mika
    Yamamoto, Kazuhiro
    Minegaki, Tetsuya
    Takegami, Shigehiko
    Takahashi, Minoru
    Yokoyama, Teruyoshi
    Okumura, Katsuhiko
    MOLECULAR MEDICINE REPORTS, 2012, 5 (03) : 603 - 609