Tubocapsanolide A inhibits transforming growth factor-beta-activating kinase 1 to suppress NF-kappaB-induced CCR7

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Updated: Jun 27, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Mei-Ren Pan1, Hui-Chiu Chang1, Yang-Chang Wu2

  • 1Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807.

The Journal of Biological Chemistry
|December 4, 2008
PubMed

Insights

Tubocapsanolide A, a plant-derived compound, inhibits breast cancer cell invasion by suppressing CCR7 expression. This natural compound may prevent the spread of breast cancer to lymph nodes.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Oncology

Background:

  • Withanolides are C(28) steroidal lactones from plants with anti-cancer properties.
  • Chemokine receptor CCR7 is crucial for cancer cell lymphatic invasion and overexpressed in metastatic breast cancer.

Purpose of the Study:

  • To investigate the effect of tubocapsanolide A (Tubo A) on CCR7 expression and breast cancer cell migration.
  • To elucidate the molecular mechanisms underlying Tubo A's action.

Main Methods:

  • Chromatin immunoprecipitation assay to assess NF-kappaB binding to the CCR7 promoter.
  • Inhibition assays for IkappaB kinase (IKK), p38 kinase, and mitogen and stress-activated protein kinase 1 (MSK1).
  • In vivo studies in mice to evaluate metastasis reduction.

Main Results:

  • Tubo A suppressed NF-kappaB-mediated CCR7 expression and attenuated breast cancer cell migration.
  • Tubo A inhibited IKK, p38, and MSK1 activities, reducing NF-kappaB activation.
  • Tubo A reduced NF-kappaB activation, CCR7 expression, and lymph node metastasis in vivo.

Conclusions:

  • Tubo A inhibits transforming growth factor-beta-activating kinase (TAK1) to repress NF-kappaB-induced CCR7 expression in breast cancer cells.
  • Tubo A shows potential for preventing lymphatic invasion in breast cancer.

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