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Updated: Jun 3, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

Alantolactone inhibits cell proliferation by interrupting the interaction between Cripto-1 and activin receptor type

Ying Shi1, Yong Li Bao, Yin Wu

  • 1National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China.

Journal of Biomolecular Screening
|March 8, 2011
PubMed

Insights

Alantolactone inhibits tumor growth by blocking the Cripto-1/activin receptor type II interaction, a key part of activin signaling. This natural compound shows tumor-specific antiproliferative effects, offering a potential new cancer treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Deregulation of activin signaling is implicated in tumor formation.
  • Cancer cells often block activin signaling via a Cripto-1, activin, and activin receptor type II (ActRII) complex.

Purpose of the Study:

  • To develop a drug screening model to identify inhibitors of the Cripto-1/ActRII interaction.
  • To evaluate the potential of natural compounds as inhibitors for cancer treatment.

Main Methods:

  • A mammalian two-hybrid system was employed to create a drug screening model.
  • 300 natural compounds were screened to identify inhibitors.
  • Activin/SMAD3 signaling and antiproliferative effects were assessed in human colon adenocarcinoma HCT-8 cells.

Main Results:

  • Alantolactone was identified as a small molecule inhibitor that interrupts the Cripto-1 and ActRII interaction.
  • Alantolactone induced activin/SMAD3 signaling in HCT-8 cells.
  • Alantolactone demonstrated tumor-specific antiproliferative effects with minimal toxicity to normal cells at 5 µg/mL, dependent on the activin/SMAD3 pathway.

Conclusions:

  • Alantolactone exerts its antitumor effect by disrupting the Cripto-1/ActRII interaction within the activin signaling pathway.
  • Targeting Cripto-1/ActRII interactions represents a promising strategy for novel cancer therapeutic development.

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