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Title: | Coleon U, Isolated from Plectranthus mutabilis Codd., Decreases P-Glycoprotein Activity Due to Mitochondrial Inhibition | Authors: | Jovanović Stojanov, Sofija Ntungwe, Epole N. Dinić, Jelena Podolski-Renić, Ana Pajović, Milica Rijo, Patrícia Pešić, Milica |
Keywords: | Coleon U; P-glycoprotein; cancer multidrug resistance | Issue Date: | 12-Jul-2023 | Publisher: | MDPI | Project: | Ministry of science, technological development and innovation of the Republic of Serbia, grant number 451-03-47/2023-01/200007 | Serial title, monograph or event: | Pharmaceutics | Volume: | 15 | Issue: | 7 | Abstract: | Multidrug resistance in cancer is often mediated by P-glycoprotein. Natural compounds have been suggested as a fourth generation of P-glycoprotein inhibitors. Coleon U, isolated from Plectranthus mutabilis Codd., was reported to modulate P-glycoprotein activity but the underlying mechanism has not yet been revealed. Therefore, the effects of Coleon U on cell viability, proliferation, and cell death induction were studied in a non-small-cell lung carcinoma model comprising sensitive and multidrug-resistant cells with P-glycoprotein overexpression. P-glycoprotein activity and mitochondrial membrane potential were assessed by flow cytometry upon Coleon U, sodium-orthovanadate (an ATPase inhibitor), and verapamil (an ATPase stimulator) treatments. SwissADME was used to identify the pharmacokinetic properties of Coleon U, while P-glycoprotein expression was studied by immunofluorescence. Our results showed that Coleon U is not a P-glycoprotein substrate and is equally efficient in sensitive and multidrug-resistant cancer cells. A decrease in P-glycoprotein activity observed with Coleon U and verapamil after 72 h is antagonized in combination with sodium-orthovanadate. Coleon U induced a pronounced effect on mitochondrial membrane depolarization and showed a tendency to decrease P-glycoprotein expression. In conclusion, Coleon U-delayed effect on the decrease in P-glycoprotein activity is due to P-glycoprotein's functioning dependence on ATP production in mitochondria. | URI: | https://hdl.handle.net/10316/112575 | ISSN: | 1999-4923 | DOI: | 10.3390/pharmaceutics15071942 | Rights: | openAccess |
Appears in Collections: | FCTUC Química - Artigos em Revistas Internacionais |
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Coleon-U-Isolated-from-Plectranthus-mutabilis-Codd-Decreases-PGlycoprotein-Activity-Due-to-Mitochondrial-InhibitionPharmaceutics.pdf | 7.73 MB | Adobe PDF | View/Open |
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