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Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their access...

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Osteosarcoma Cell and Osteosarcoma Stem Cell Potent Immunogenic Bi-Nuclear Gallium(III) Complexes.

Xiao Feng1, Shruti Dhandore1, Yu Liu1

  • 1School of Chemistry, University of Leicester, Leicester, LE1 7RH, UK.

Chemistry (Weinheim an Der Bergstrasse, Germany)
|April 9, 2025
PubMed
Summary

New gallium(III) complexes show potent anti-cancer activity against osteosarcoma cells and stem cells (OSCs). These compounds effectively target 3D tumor structures and exhibit promising immunogenic properties, representing a novel therapeutic approach.

Keywords:
Schiff basesantitumor agentsbioinorganic chemistrycancergallium

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Area of Science:

  • Inorganic Chemistry
  • Medicinal Chemistry
  • Cancer Biology

Background:

  • Osteosarcoma is a primary bone cancer with limited treatment options.
  • Current metallodrugs like cisplatin and carboplatin have significant limitations in treating osteosarcoma, especially its stem cell population.
  • Osteosarcoma stem cells (OSCs) are crucial for tumor recurrence and metastasis.

Purpose of the Study:

  • To synthesize and characterize novel bi-nuclear gallium(III) complexes.
  • To evaluate the anti-cancer efficacy of these complexes against osteosarcoma cells and OSCs.
  • To investigate the mechanism of action and immunogenic potential of the most effective gallium(III) complex.

Main Methods:

  • Synthesis and characterization of bi-nuclear gallium(III) complexes with Schiff base ligands and 8-hydroxyquinoline.
  • Monolayer and 3D sarcosphere cytotoxicity assays.
  • Caspase-dependent apoptosis and paraptosis assays.
  • Phagocytosis assays by immune cells.

Main Results:

  • Gallium(III) complexes 1-4 demonstrated micromolar cytotoxicity against osteosarcoma cells and OSCs.
  • Complex 2 showed superior potency against OSCs (up to 13-fold) and sarcospheres (up to 53-fold) compared to cisplatin and carboplatin.
  • Complex 2 induced caspase-dependent apoptosis and paraptosis, leading to immunogenic cell death.
  • Treated cells were effectively phagocytosed by immune cells, indicating significant immunogenic potential.

Conclusions:

  • Bi-nuclear gallium(III) complexes exhibit potent anti-osteosarcoma and anti-OSC activities.
  • These complexes show enhanced efficacy against 3D tumor structures, suggesting better drug penetration.
  • Gallium(III) complex 2 is the first metal complex to demonstrate an immunogenic response against both bulk osteosarcoma cells and OSCs, offering a novel therapeutic strategy.