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Related Experiment Video

Updated: Jun 25, 2025

In vitro Enrichment of Ovarian Cancer Tumor-initiating Cells
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In-cell Catalysis by Tethered Organo-Osmium Complexes Generates Selectivity for Breast Cancer Cells.

J P C Coverdale1,2, R A Bedford1, O W L Carter2

  • 1School of Pharmacy, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, B15 2TT, UK.

Chembiochem : a European Journal of Chemical Biology
|May 24, 2024
PubMed
Summary
This summary is machine-generated.

A novel osmium catalyst overcomes drug resistance in triple-negative breast cancer cells. This stable, tethered catalyst works via in-cell hydrogenation and generates reactive oxygen species, selectively targeting cancer cells.

Keywords:
cancerin-cell catalysisosmiumredoxtransfer hydrogenation

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Area of Science:

  • Organometallic Chemistry
  • Cancer Therapeutics
  • Catalysis

Background:

  • Drug resistance is a major challenge in cancer therapy.
  • Catalytic anticancer agents offer multi-targeting strategies but face deactivation issues.
  • Osmium-based catalysts show promise but require improved stability and targeted delivery.

Purpose of the Study:

  • To synthesize a stable, potent osmium-based catalyst for cancer treatment.
  • To investigate the catalyst's mechanism of action and cellular uptake.
  • To evaluate the catalyst's efficacy against triple-negative breast cancer and tamoxifen resistance.

Main Methods:

  • Synthesis of a tethered Os-based 16-electron half-sandwich catalyst.
  • Antiproliferative activity assays against triple-negative breast cancer cells.
  • Speciation and cellular accumulation studies (albumin binding, energy-dependent uptake).
  • In-cell transfer hydrogenation catalysis with sodium formate.
  • Reactive oxygen species (ROS) generation assays.

Main Results:

  • The tethered Os catalyst demonstrated potent antiproliferative activity, comparable to cisplatin.
  • The catalyst effectively overcame tamoxifen resistance in cancer cells.
  • Osmium was primarily albumin-bound extracellularly and taken up via an energy-dependent, protein-mediated pathway.
  • The catalyst remained intact upon cellular delivery and catalyzed in-cell transfer hydrogenation.
  • The mechanism involved ROS generation, showing selectivity for cancer cells.

Conclusions:

  • A stable, tethered Os-based catalyst offers a promising strategy for overcoming drug resistance in triple-negative breast cancer.
  • The catalyst's efficacy is linked to its ability to perform in-cell catalysis and induce ROS.
  • Albumin-mediated uptake and intracellular delivery are key to the catalyst's function.