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Updated: Jun 16, 2026

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations
10:26

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations

Published on: November 7, 2019

Increased ubiquitination of multidrug resistance 1 by ginsenoside Rd

Yuba Raj Pokharel1, Nak Doo Kim, Hyo-Kyung Han

  • 1BK21 Project Team, College of Pharmacy, Chosun University, Gwangju 501-759, South Korea.

Nutrition and Cancer
|January 26, 2010
PubMed

Insights

Ginsenosides, particularly ginsenoside Rd, reduce multidrug resistance protein levels in chemotherapy-resistant breast cancer cells. This suggests ginseng may enhance anti-cancer treatments by overcoming drug resistance.

Area of Science:

  • Pharmacology and Molecular Biology
  • Cancer Research
  • Natural Products Chemistry

Background:

  • MCF-7/ADR cells, a human breast cancer line, exhibit multidrug resistance (MDR) through MDR1 gene overexpression.
  • This resistance limits the efficacy of chemotherapeutic agents like doxorubicin, anthracylines, and taxol.

Purpose of the Study:

  • To investigate the effect of ginsenosides on MDR1 gene expression in doxorubicin-resistant breast cancer cells.
  • To determine if ginsenosides can reverse chemotherapy resistance mediated by MDR1.

Main Methods:

  • Treatment of MCF-7/ADR cells with specific ginsenosides (Rd, Re, Rb1, Rg1) at 100 microg/ml.
  • Assessment of MDR1 protein and mRNA levels, key transcriptional factors, and reporter gene activity.
  • Analysis of MDR1 protein ubiquitination and subsequent degradation.
  • Evaluation of doxorubicin resistance reversal by ginsenoside Rd.

Main Results:

  • Ginsenosides Rd, Re, Rb1, and Rg1 significantly decreased MDR1 protein levels without cytotoxicity.
  • Ginsenoside Rd was the most potent inhibitor of MDR1 protein expression.
  • Ginsenoside Rd did not alter MDR1 mRNA levels or key transcriptional factors, suggesting post-transcriptional regulation.
  • Ginsenoside Rd increased MDR1 ubiquitination, indicating enhanced protein degradation.
  • Ginsenoside Rd treatment reversed doxorubicin resistance in MCF-7/ADR cells.

Conclusions:

  • Ginsenosides, especially Rd, effectively down-regulate MDR1 protein levels in resistant breast cancer cells.
  • The mechanism involves enhanced ubiquitin-dependent protein degradation of MDR1, not altered gene transcription.
  • Ginseng administration may be a valuable adjunct therapy for chemotherapy-resistant breast cancer by overcoming MDR1-mediated resistance.

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