Diallyl disulfide inhibits colon cancer metastasis by suppressing Rac1-mediated epithelial-mesenchymal transition

Longzheng Xia1, Jingguan Lin1, Jian Su2

  • 1Key Laboratory of Translational Radiation Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University and Hunan Cancer Hospital, Changsha 410013, Hunan, People's Republic of China.

Oncotargets and Therapy
|August 15, 2019
PubMed
Abstract

Insights

Diallyl disulfide (DADS) suppresses colon cancer metastasis by inhibiting Rac1 expression and epithelial-mesenchymal transition (EMT). This study elucidates the molecular mechanisms underlying DADS

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Epithelial-mesenchymal transition (EMT) is a key driver of tumor metastasis, presenting a therapeutic target.
  • Diallyl disulfide (DADS) has shown potential in suppressing colon cancer cell migration and invasion by inhibiting Ras related C3 botulinum toxin substrate1 (Rac1).

Purpose of the Study:

  • To investigate the underlying mechanisms by which DADS inhibits Rac1 expression and its role in colon cancer metastasis.
  • To explore Rac1 as a potential therapeutic target for colon cancer treatment.

Main Methods:

  • Detection of Rac1 and EMT markers (vimentin, N-cadherin, E-cadherin) in colon cancer samples and cell lines.
  • In vitro and in vivo assays to assess cell migration, invasion, and metastasis.
  • Analysis of signaling pathways, including PI3K/Akt and Rac1-mediated PAK1-LIMK1-Cofilins.

Main Results:

  • Rac1 overexpression correlates with aberrant EMT markers and poor prognosis in colon cancer.
  • DADS suppresses Rac1 expression and activity by inhibiting the PI3K/Akt pathway, thereby reducing EMT, invasion, and migration.
  • DADS blocks EMT through the Rac1-mediated PAK1-LIMK1-Cofilins signaling pathway.

Conclusions:

  • Rac1 is a critical mediator of EMT, invasion, and metastasis in colon cancer.
  • DADS effectively inhibits colon cancer progression by targeting Rac1 and its downstream signaling pathways.
  • Rac1 represents a promising molecular target for DADS-based anti-cancer therapies.

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