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Silver(I) Bromide Phosphines Induce Mitochondrial-Mediated Apoptosis in Malignant Human Colorectal Cells

Kim Elli Roberts1, Zelinda Engelbrecht1, Kariska Potgieter2

  • 1School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg 2050, South Africa.

Biomedicines
|October 28, 2023
PubMed

Insights

Novel silver complexes show promise for colon cancer treatment. Complex 1 effectively inhibits cancer cell growth and induces apoptosis with minimal toxicity to healthy cells, offering a potential new therapeutic strategy.

Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Nanotechnology

Background:

  • Colorectal cancer presents a significant therapeutic challenge due to emerging resistance to existing treatments.
  • Silver compounds are recognized for their antimicrobial and anti-cancer properties, suggesting potential in cancer therapy.

Purpose of the Study:

  • To synthesize and characterize novel silver(I) phosphine complexes for antiproliferative activity.
  • To evaluate the efficacy and selectivity of these complexes against human colorectal cancer cells in vitro.

Main Methods:

  • Synthesis and characterization of two silver(I) phosphine complexes using elemental analysis, IR, and NMR spectroscopy.
  • In vitro antiproliferative assays on HT-29 colorectal cancer cells, including morphological analysis, alamarBlue® proliferation assay, and flow cytometry.
  • Assessment of mitochondrial alterations and induction of regulated cell death.

Main Results:

  • Complex 1 ([silver(I) diphenyl-2-pyridylphosphine]Br) demonstrated significant selective inhibition of HT-29 cells with minimal toxicity to HEK-293 and MRHF cells.
  • Complex 1 exhibited superior efficacy (IC50, 7.49 µM) compared to complex 2 (IC50, 21.75 µM) and cisplatin (CDDP, IC50, 200.96 µM) in inhibiting cell proliferation.
  • Flow cytometry revealed that complex 1 induces apoptosis via mitochondrial pathways, characterized by morphological changes, increased ROS, and mitochondrial depolarization.

Conclusions:

  • Complex 1 is a promising novel metal-based therapeutic agent for colorectal cancer.
  • The compound selectively targets cancer cells and induces apoptosis, suggesting a potential new treatment strategy.
  • Further investigation into complex 1's mechanism and efficacy is warranted for clinical translation.
Keywords:
HT-29anti-cancerapoptosisflow cytometrymitochondriasilver(I) bromide phosphine

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