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Andrographolide reverts multidrug resistance in KBCh R 8-5 cells through AKT signaling pathway.
- Source :
-
Cell biochemistry and function [Cell Biochem Funct] 2024 Mar; Vol. 42 (2), pp. e3948. - Publication Year :
- 2024
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Abstract
- Multidrug resistance (MDR) is a major obstacle in cancer chemotherapy. P-glycoprotein (P-gp) one of the ATP-binding cassette (ABC) transporters plays an important role in MDR. In this study, we examined the sensitizing property of andrographolide (Andro) to reverse MDR in the drug-resistant KBCh <superscript>R</superscript> 8-5 cells. Andro exhibited increased cytotoxicity in a concentration-dependent manner in the P-gp overexpressing KBCh <superscript>R</superscript> 8-5 cells. Furthermore, Andro showed synergistic interactions with PTX and DOX in this drug-resistant cells. Andro co-administration enhanced PTX- and DOX-induced cytotoxicity and reduced cell proliferation in the MDR cancer cells. Moreover, reactive oxygen species (ROS) were elevated with a decrease in the mitochondrial membrane potential (MMP) during Andro and chemotherapeutic drugs combination treatment in the drug-resistant cells. Furthermore, Andro and PTX-induced cell cycle arrest was observed in the drug-resistant cell. We also noticed that the expression of ABCB1 and AKT were downregulated during Andro (4 µM) treatment. Furthermore, Andro treatment enhanced the expression of caspase 3 and caspase 9 in the combinational groups that support the enhanced apoptotic cell death in drug-resistant cancer cells. Therefore, the results reveal that Andro plays a role in the reversal of P-gp-mediated MDR in KBCh <superscript>R</superscript> 8-5 cells which might be due to regulating ABCB1/AKT signaling pathway.<br /> (© 2024 John Wiley & Sons Ltd.)
Details
- Language :
- English
- ISSN :
- 1099-0844
- Volume :
- 42
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell biochemistry and function
- Publication Type :
- Academic Journal
- Accession number :
- 38379216
- Full Text :
- https://doi.org/10.1002/cbf.3948