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Updated: Jan 30, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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The palladacycle complex AJ-5 induces apoptotic cell death while reducing autophagic flux in rhabdomyosarcoma cells

Jenna Susan Bleloch1, André du Toit2, Liezl Gibhard3

  • 11Division of Cell Biology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, Western Cape South Africa.

Cell Death Discovery
|February 1, 2019
PubMed

Insights

A novel compound, AJ-5, shows potent anti-cancer activity against rhabdomyosarcoma (RMS) by inducing DNA damage, cell cycle arrest, and apoptosis. Pharmacokinetic studies in mice indicate AJ-5

Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Pharmacology

Background:

  • Rhabdomyosarcoma (RMS) is the most common childhood soft tissue sarcoma with poor outcomes for metastatic disease.
  • Current treatments for RMS have debilitating side effects and limited efficacy.
  • A novel binuclear palladacycle, AJ-5, has shown promise in other cancers with minimal adverse effects.

Purpose of the Study:

  • To investigate the anti-cancer activity and mechanism of action of AJ-5 in alveolar and embryonal RMS.
  • To evaluate the pharmacokinetic properties of AJ-5 in mice.

Main Methods:

  • In vitro cytotoxicity assays (IC50, selectivity index) and cell-based assays (clonogenic, migration).
  • Western blotting for DNA damage response proteins, cell cycle regulators, and stress pathways.
  • Flow cytometry for apoptosis and necrosis detection; assessment of autophagic flux.
  • Pharmacokinetic studies in mice.

Main Results:

  • AJ-5 demonstrated potent cytotoxicity against RMS cells (IC50 ≤ 0.2 µM) with a favorable selectivity index (>2).
  • AJ-5 inhibited RMS cell survival and migration, induced DNA damage response (γH2AX, p-ATM, p-Chk2), and G1 cell cycle arrest via p21.
  • AJ-5 triggered apoptosis and necrosis, reduced autophagic flux, and exhibited favorable pharmacokinetic properties in mice (good half-life, low clearance, good absorption).

Conclusions:

  • AJ-5 exhibits significant anti-cancer activity against rhabdomyosarcoma through multiple mechanisms, including DNA damage induction and apoptosis.
  • The favorable pharmacokinetic profile suggests AJ-5's potential as a chemotherapeutic agent for drug-resistant and advanced sarcomas.
  • AJ-5 represents a promising candidate for further development in treating pediatric and adolescent sarcomas.

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