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The natural compound neobractatin inhibits tumor metastasis by upregulating the RNA-binding-protein MBNL2

Juan Zhang1,2, Zhaoqing Zheng1,2, Man Wu1,2

  • 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, P.R. China.

Cell Death & Disease
|July 20, 2019
PubMed

Insights

Neobractatin (NBT) inhibits breast and lung cancer metastasis by upregulating Muscleblind-like 2 (MBNL2). This natural compound targets the pAKT/epithelial-mesenchymal transition (EMT) pathway, offering a potential new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Natural Products Chemistry

Background:

  • Tumor metastasis is a primary driver of cancer-related mortality.
  • Neobractatin (NBT), a compound from Garcinia bracteata, shows potential in inhibiting cancer metastasis.
  • The precise mechanisms by which NBT exerts its antimetastatic effects are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying NBT's antimetastatic activity.
  • To investigate the role of Muscleblind-like 2 (MBNL2) in NBT-mediated cancer metastasis inhibition.
  • To explore the involvement of the pAKT/epithelial-mesenchymal transition (EMT) pathway.

Main Methods:

  • RNA-sequencing and transcriptome analysis to identify NBT-modulated genes.
  • Bioinformatic analysis of The Cancer Genome Atlas (TCGA) database for MBNL2 expression.
  • In vitro studies involving MBNL2 overexpression and knockdown in cancer cell lines.
  • In vivo metastasis assays using a mouse xenograft model.

Main Results:

  • MBNL2 was significantly upregulated in cancer cells treated with NBT and downregulated in tumor tissues compared to normal tissues.
  • MBNL2 overexpression mimicked NBT's antimetastatic effects and enhanced NBT's efficacy, while MBNL2 knockdown reversed these effects.
  • NBT and MBNL2 mediated antimetastasis through the pAKT/EMT signaling pathway.
  • Both NBT and MBNL2 demonstrated metastasis inhibition in vivo.

Conclusions:

  • NBT exhibits significant antitumor and antimetastatic activity in breast and lung cancers.
  • MBNL2 plays a crucial role in mediating NBT's antimetastatic effects.
  • The pAKT/EMT pathway is a key target for NBT and MBNL2 in suppressing cancer metastasis.

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