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Natural Products as Modulators of ABC Transporters in Breast Cancer

Yoganishalini Sagadevan1, Reyhaneh Farghadani1,2, Ammu K Radhakrishnan1

  • 1Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Sunway City, Malaysia.

Phytotherapy Research : PTR
|May 13, 2026
PubMed

Insights

Natural products can overcome breast cancer multidrug resistance (MDR) by inhibiting ATP-binding cassette (ABC) transporters. These compounds enhance chemotherapy efficacy and reduce toxicity, offering new therapeutic strategies for aggressive breast cancer subtypes.

Area of Science:

  • Oncology
  • Pharmacology
  • Natural Product Chemistry

Background:

  • Breast cancer, especially triple-negative breast cancer (TNBC), faces treatment challenges due to multidrug resistance (MDR).
  • ATP-binding cassette (ABC) transporters (e.g., P-gp, BCRP, MRP1) are key drivers of MDR by actively exporting chemotherapeutic drugs.
  • This efflux reduces intracellular drug concentrations, leading to treatment failure and poor patient outcomes.

Purpose of the Study:

  • To review the potential of natural products in overcoming MDR in breast cancer by targeting ABC transporters.
  • To explore the mechanisms by which natural products modulate ABC transporter activity and related pathways.
  • To assess the synergistic effects of natural products with conventional chemotherapy in breast cancer treatment.

Main Methods:

  • A comprehensive literature search was performed across major scientific databases (Ovid Medline, PubMed, Scopus, Embase, Web of Science, EBSCOhost).
  • Articles were screened using a two-stage process (title/abstract and full text review), supplemented by reference list searches.
  • The review synthesized findings on natural product interactions with ABC transporters and MDR-related pathways.

Main Results:

  • Natural products inhibit ABC transporters via suppression of protein and mRNA expression, and direct inhibition of drug efflux.
  • These compounds modulate indirect regulatory pathways, including NF-κB, YB-1, PI3K/Akt signaling, and ATPase activity.
  • Natural products demonstrate synergistic effects with chemotherapeutics like doxorubicin and paclitaxel, enhancing drug efficacy and reducing toxicity.

Conclusions:

  • Natural products show significant promise as adjunct therapies to reverse MDR in breast cancer.
  • Targeting ABC transporters with natural compounds offers a novel strategy to improve treatment outcomes for resistant breast cancer.
  • Further research into these natural agents could lead to improved therapeutic regimens and better patient survival rates.
Keywords:
ATP‐binding cassette (ABC) transporterschemotherapy resistancedrug efflux proteinsmultidrug resistance (MDR)natural products

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