Andrographolide reverts multidrug resistance in KBCh R 8-5 cells through AKT signaling pathway.
Deepa S LakraPradhapsingh BharathirajaT DhanalakshmiNagarajan Rajendra PrasadPublished in: Cell biochemistry and function (2024)
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 R 8-5 cells. Andro exhibited increased cytotoxicity in a concentration-dependent manner in the P-gp overexpressing KBCh R 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 R 8-5 cells which might be due to regulating ABCB1/AKT signaling pathway.
Keyphrases
- drug resistant
- cell cycle arrest
- multidrug resistant
- cell death
- induced apoptosis
- signaling pathway
- pi k akt
- acinetobacter baumannii
- cell proliferation
- endoplasmic reticulum stress
- reactive oxygen species
- stem cells
- dna damage
- mesenchymal stem cells
- binding protein
- single cell
- climate change
- combination therapy
- endothelial cells
- cell therapy
- cell migration
- dna binding
- transcription factor
- human health
- squamous cell