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The platinum coordination complex inhibits cell invasion-migration and epithelial-to-mesenchymal transition by

Maha-Hamadien Abdulla1, Aminah Ahmad Alzailai2, Mansoor-Ali Vaali-Mohammed1

  • 1Colorectal Research Chair, Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Frontiers in Pharmacology
|November 29, 2023
PubMed

Insights

A novel platinum (PT) complex effectively inhibits colorectal cancer (CRC) cell migration and invasion by modulating transforming growth factor-beta (TGF-β) signaling and epithelial-to-mesenchymal transition (EMT) markers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Medicinal Chemistry

Background:

  • Colorectal cancer (CRC) incidence is rising globally, with metastasis present in 20% of diagnoses.
  • Transforming growth factor-beta (TGF-β) signaling drives epithelial-to-mesenchymal transition (EMT), crucial for CRC progression and metastasis.

Purpose of the Study:

  • To investigate the effect of a novel platinum (salicylaldiminato) PT(II) complex (PT-complex) on TGF-β and EMT markers in human CRC cell lines.
  • To assess the PT-complex's impact on CRC cell invasion and migration.

Main Methods:

  • Functional studies and wound healing assays were employed to evaluate cell motility, migration, and invasion.
  • Western blotting was used to analyze the expression of EMT markers with and without TGF-β stimulation.
  • Microarray analysis identified differentially expressed genes related to invasion and migration.

Main Results:

  • The PT-complex significantly reduced CRC cell migration and invasion.
  • PT-complex upregulated E-cadherin and downregulated N-Cadherin and Vimentin, key EMT markers.
  • SMAD3 activation was significantly suppressed by the PT-complex in both CRC cell lines.

Conclusions:

  • The novel PT-complex exhibits antiproliferative activity and reduces CRC cell metastasis.
  • The PT-complex modulates TGF-β-regulated EMT markers, offering a potential therapeutic strategy for CRC.
  • These findings elucidate the molecular mechanism of the PT-complex's antitumoral properties via TGF-β/SMAD signaling.
Keywords:
TGF-βcolorectal cancerepithelial-to-mesenchymal transitionmetastasisplatinum

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