Chemosensitizing potential of andrographolide in P-glycoprotein overexpressing multidrug-resistant cancer cell lines

Nat Prod Res. 2024 Mar;38(6):941-946. doi: 10.1080/14786419.2023.2208261. Epub 2023 May 5.

Abstract

The P-glycoprotein (P-gp) plays a major role in the efflux of chemotherapeutic drugs and significantly limits chemotherapy efficacy. Chemosensitizers augment the therapeutic effects of anticancer agents by overcoming drug resistance mechanisms. In this study, the chemosensitizing property of andrographolide (Andro) in P-gp overexpressing multidrug-resistant (MDR) colchicine-selected KBChR 8-5 cells was evaluated. Molecular docking studies showed Andro exhibits higher binding interaction with P-gp than the other two ABC-transporters studied. Further, it inhibits P-gp transport function in a concentration dependant manner in the colchicine-selected KBChR 8-5 cells. Moreover, Andro downregulates P-gp overexpression via NF-κB signaling in these MDR cell lines. MTT-based cell-based assay illustrates that Andro treatment augments the PTX effect in the KBChR 8-5 cells. Further, the Andro plus PTX combination showed enhanced apoptotic cell death in KBChR 8-5 cells compared with PTX alone treatment. Therefore, the results showed that Andro enhances PTX therapeutic effect in the drug-resistant KBChR 8-5 cells.

Keywords: Multidrug resistance; P-glycoprotein; andrographolide; chemosensitization; nuclear factor-κB.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1*
  • Cell Line
  • Colchicine
  • Diterpenes*
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Humans
  • Molecular Docking Simulation
  • Neoplasms*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • andrographolide
  • ATP Binding Cassette Transporter, Subfamily B
  • Colchicine
  • Diterpenes