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The cell-penetrating FOXM1 N-terminus (M1-138) demonstrates potent inhibitory effects on cancer cells by targeting

Zhenwang Zhang1, Huitong Bu1, Jingwei Yu1

  • 1State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Hunan Engineering Research Center for Anticancer Targeted Protein Pharmaceuticals, Hunan University, Changsha, Hunan 410082, China.

Theranostics
|June 28, 2019
PubMed

Insights

A novel compound, M1-138, effectively inhibits cancer cell proliferation and migration by targeting transcription factor FOXM1 and its interaction with SMAD3. This therapeutic strategy shows promise for developing new anti-cancer drugs.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Drug Development

Background:

  • Transcription factor FOXM1 is crucial for cell proliferation, DNA repair, and cancer metastasis.
  • Inhibiting FOXM1 can prevent cancer initiation and progression, making it a key therapeutic target.
  • The N-terminus of FOXM1 regulates its transcriptional activity and interaction with SMAD3.

Purpose of the Study:

  • To investigate the anti-cancer effects of a novel recombinant FOXM1 N-terminal domain (1-138aa) fused with a cell-penetrating peptide, named M1-138.
  • To analyze the impact of M1-138 on cancer cell proliferation, migration, and tumorigenicity.
  • To elucidate the molecular mechanisms underlying M1-138's anti-cancer activity.

Main Methods:

  • Production of M1-138 using an E. coli expression system.
  • In vitro analysis of cancer cell proliferation, migration, and colony formation.
  • Assays to evaluate DNA binding, transcriptional activity, protein interactions, and mRNA/protein levels.
  • In vivo studies using nude mouse xenograft models.

Main Results:

  • M1-138 significantly reduced cancer cell proliferation and migration.
  • The compound attenuated FOXM1 transcriptional activity by interfering with FOXM1 and SMAD3 interaction.
  • M1-138 inhibited tumor growth in vivo without observable toxicity.

Conclusions:

  • M1-138 demonstrates potent anti-cancer properties by targeting FOXM1 and SMAD3.
  • The compound effectively inhibits cancer cell proliferation, migration, and tumorigenicity.
  • M1-138 represents a promising drug candidate for developing novel anti-cancer therapeutics.
Keywords:
Anticancer protein therapeuticsCell-penetrating peptideTargets for tumor suppressionTranscription factor FOXM1

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