Dioscin restores the activity of the anticancer agent adriamycin in multidrug-resistant human leukemia K562/adriamycin cells by down-regulating MDR1 via a mechanism involving NF-κB signaling inhibition

J Nat Prod. 2013 May 24;76(5):909-14. doi: 10.1021/np400071c. Epub 2013 Apr 26.


The purpose of this study was to investigate the ameliorating effect of dioscin (1) on multidrug resistance (MDR) in adriamycin (ADR)-resistant erythroleukemic cells (K562/adriamycin, K562/ADR) and to clarify the molecular mechanisms involved. High levels of multidrug resistance 1 (MDR1) mRNA and protein and reduced ADR retention were found in K562/ADR cells compared with parental cells (K562). Dioscin (1), a constituent of plants in the genus Discorea, significantly inhibited MDR1 mRNA and protein expression and MDR1 promoter and nuclear factor κ-B (NF-κB) activity in K562/ADR cells. MDR1 mRNA and protein suppression resulted in the subsequent recovery of intracellular drug accumulation. Additionally, inhibitor κB-α (IκB-α) degradation was inhibited by 1. Dioscin (1) reversed ADR-induced MDR by down-regulating MDR1 expression by a mechanism that involves the inhibition of the NF-κB signaling pathway. These findings provide evidence to support the further investigation of the clinical application of dioscin (1) as a chemotherapy adjuvant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antineoplastic Agents / pharmacology
  • Base Sequence
  • Dioscorea / chemistry
  • Diosgenin / analogs & derivatives*
  • Diosgenin / chemistry
  • Diosgenin / pharmacology
  • Doxorubicin / analysis
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Resistance, Multiple / drug effects*
  • Drug Resistance, Neoplasm / drug effects
  • Humans
  • I-kappa B Proteins / drug effects
  • K562 Cells
  • Leukemia, Erythroblastic, Acute / drug therapy
  • Luciferases / metabolism
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors*
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • RNA, Messenger
  • NF-KappaB Inhibitor alpha
  • dioscin
  • Doxorubicin
  • Luciferases
  • Diosgenin