Pinostrobin and Tectochrysin Conquer Multidrug-Resistant Cancer Cells via Inhibiting P-Glycoprotein ATPase
Enhanced drug efflux through ATP-binding cassette transporters, particularly P-glycoprotein (P-gp), is a key mechanism underlying multidrug resistance (MDR). In the present study, we investigated the inhibitory effects of pinostrobin and tectochrysin on P-gp in MDR cancer cells and the underlying me...
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Published in | Pharmaceuticals (Basel, Switzerland) Vol. 16; no. 2; p. 205 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
MDPI AG
29.01.2023
MDPI |
Subjects | |
Online Access | Get full text |
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Summary: | Enhanced drug efflux through ATP-binding cassette transporters, particularly P-glycoprotein (P-gp), is a key mechanism underlying multidrug resistance (MDR). In the present study, we investigated the inhibitory effects of pinostrobin and tectochrysin on P-gp in MDR cancer cells and the underlying mechanisms. Fluorescence substrate efflux assays, multidrug resistance 1 (MDR1) shift assays, P-gp ATPase activity assays, Western blotting, and docking simulation were performed. The potential of the test compounds for MDR reversal and the associated molecular mechanisms were investigated through cell viability assay, cell cycle analysis, apoptosis assay, and further determining the combination index. Results demonstrated that pinostrobin and tectochrysin were not the substrates of P-gp, nor did they affect the expression of this transporter. Both compounds noncompetitively inhibited the efflux of rhodamine 123 and doxorubicin through P-gp. Furthermore, they resensitized MDR cancer cells to chemotherapeutic drugs, such as vincristine, paclitaxel, and docetaxel; thus, they exhibited strong MDR reversal effects. Our findings indicate that pinostrobin and tectochrysin are effective P-gp inhibitors and promising candidates for resensitizing MDR cancer cells. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. |
ISSN: | 1424-8247 1424-8247 |
DOI: | 10.3390/ph16020205 |