Isobavachalcone as an Active Membrane Perturbing Agent and Inhibitor of ABCB1 Multidrug Transporter
Isobavachalcone (IBC) is an active substance from the medicinal plant <i>Psoralea corylifolia</i>. This prenylated chalcone was reported to possess antioxidative, anti-inflammatory, antibacterial, and anticancer activities. Multidrug resistance (MDR) associated with the over-expression o...
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doaj-1f8451e8086944fd8cd9ed02710c9b222021-08-06T15:29:23ZengMDPI AGMolecules1420-30492021-07-01264637463710.3390/molecules26154637Isobavachalcone as an Active Membrane Perturbing Agent and Inhibitor of ABCB1 Multidrug TransporterAnna Palko-Łabuz0Maria Błaszczyk1Kamila Środa-Pomianek2Olga Wesołowska3Department of Biophysics and Neuroscience, Wroclaw Medical University, ul. Chalubinskiego 3a, 50-368 Wroclaw, PolandDepartment of Biophysics and Neuroscience, Wroclaw Medical University, ul. Chalubinskiego 3a, 50-368 Wroclaw, PolandDepartment of Biophysics and Neuroscience, Wroclaw Medical University, ul. Chalubinskiego 3a, 50-368 Wroclaw, PolandDepartment of Biophysics and Neuroscience, Wroclaw Medical University, ul. Chalubinskiego 3a, 50-368 Wroclaw, PolandIsobavachalcone (IBC) is an active substance from the medicinal plant <i>Psoralea corylifolia</i>. This prenylated chalcone was reported to possess antioxidative, anti-inflammatory, antibacterial, and anticancer activities. Multidrug resistance (MDR) associated with the over-expression of the transporters of vast substrate specificity such as ABCB1 (P-glycoprotein) belongs to the main causes of cancer chemotherapy failure. The cytotoxic, MDR reversing, and ABCB1-inhibiting potency of isobavachalcone was studied in two cellular models: human colorectal adenocarcinoma HT29 cell line and its resistant counterpart HT29/Dx in which doxorubicin resistance was induced by prolonged drug treatment, and the variant of MDCK cells transfected with the human gene encoding ABCB1. Because MDR modulators are frequently membrane-active substances, the interaction of isobavachalcone with model phosphatidylcholine bilayers was studied by means of differential scanning calorimetry. Molecular modeling was employed to characterize the process of membrane permeation by isobavachalcone. IBC interacted with ABCB1 transporter, being a substrate and/or competitive inhibitor of ABCB1. Moreover, IBC intercalated into model membranes, significantly affecting the parameters of their main phospholipid phase transition. It was concluded that isobavachalcone interfered both with the lipid phase of cellular membrane and with ABCB1 transporter, and for this reason, its activity in MDR cancer cells was presumptively beneficial.https://www.mdpi.com/1420-3049/26/15/4637isobavachalconeprenylated chalconemultidrug resistance (MDR)P-glycoprotein (ABCB1MDR1)model membrane |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna Palko-Łabuz Maria Błaszczyk Kamila Środa-Pomianek Olga Wesołowska |
spellingShingle |
Anna Palko-Łabuz Maria Błaszczyk Kamila Środa-Pomianek Olga Wesołowska Isobavachalcone as an Active Membrane Perturbing Agent and Inhibitor of ABCB1 Multidrug Transporter Molecules isobavachalcone prenylated chalcone multidrug resistance (MDR) P-glycoprotein (ABCB1 MDR1) model membrane |
author_facet |
Anna Palko-Łabuz Maria Błaszczyk Kamila Środa-Pomianek Olga Wesołowska |
author_sort |
Anna Palko-Łabuz |
title |
Isobavachalcone as an Active Membrane Perturbing Agent and Inhibitor of ABCB1 Multidrug Transporter |
title_short |
Isobavachalcone as an Active Membrane Perturbing Agent and Inhibitor of ABCB1 Multidrug Transporter |
title_full |
Isobavachalcone as an Active Membrane Perturbing Agent and Inhibitor of ABCB1 Multidrug Transporter |
title_fullStr |
Isobavachalcone as an Active Membrane Perturbing Agent and Inhibitor of ABCB1 Multidrug Transporter |
title_full_unstemmed |
Isobavachalcone as an Active Membrane Perturbing Agent and Inhibitor of ABCB1 Multidrug Transporter |
title_sort |
isobavachalcone as an active membrane perturbing agent and inhibitor of abcb1 multidrug transporter |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2021-07-01 |
description |
Isobavachalcone (IBC) is an active substance from the medicinal plant <i>Psoralea corylifolia</i>. This prenylated chalcone was reported to possess antioxidative, anti-inflammatory, antibacterial, and anticancer activities. Multidrug resistance (MDR) associated with the over-expression of the transporters of vast substrate specificity such as ABCB1 (P-glycoprotein) belongs to the main causes of cancer chemotherapy failure. The cytotoxic, MDR reversing, and ABCB1-inhibiting potency of isobavachalcone was studied in two cellular models: human colorectal adenocarcinoma HT29 cell line and its resistant counterpart HT29/Dx in which doxorubicin resistance was induced by prolonged drug treatment, and the variant of MDCK cells transfected with the human gene encoding ABCB1. Because MDR modulators are frequently membrane-active substances, the interaction of isobavachalcone with model phosphatidylcholine bilayers was studied by means of differential scanning calorimetry. Molecular modeling was employed to characterize the process of membrane permeation by isobavachalcone. IBC interacted with ABCB1 transporter, being a substrate and/or competitive inhibitor of ABCB1. Moreover, IBC intercalated into model membranes, significantly affecting the parameters of their main phospholipid phase transition. It was concluded that isobavachalcone interfered both with the lipid phase of cellular membrane and with ABCB1 transporter, and for this reason, its activity in MDR cancer cells was presumptively beneficial. |
topic |
isobavachalcone prenylated chalcone multidrug resistance (MDR) P-glycoprotein (ABCB1 MDR1) model membrane |
url |
https://www.mdpi.com/1420-3049/26/15/4637 |
work_keys_str_mv |
AT annapalkołabuz isobavachalconeasanactivemembraneperturbingagentandinhibitorofabcb1multidrugtransporter AT mariabłaszczyk isobavachalconeasanactivemembraneperturbingagentandinhibitorofabcb1multidrugtransporter AT kamilasrodapomianek isobavachalconeasanactivemembraneperturbingagentandinhibitorofabcb1multidrugtransporter AT olgawesołowska isobavachalconeasanactivemembraneperturbingagentandinhibitorofabcb1multidrugtransporter |
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