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17-AAG and Apoptosis, Autophagy, and Mitophagy in Canine Osteosarcoma Cell Lines

M Massimini1, C Palmieri2, R De Maria3

  • 11 Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.

Veterinary Pathology
|April 26, 2017
PubMed

Insights

Canine osteosarcoma cells show varied responses to Hsp90 inhibitor 17-AAG. Understanding these differences in apoptosis, autophagy, and mitophagy is crucial for developing effective chemotherapy for resistant canine tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Canine osteosarcoma exhibits high resistance to conventional chemotherapy, necessitating research into underlying resistance mechanisms.
  • Heat shock protein 90 (Hsp90) is a potential therapeutic target in cancer, with inhibitors like 17-AAG (17-allylamino-17-demethoxygeldanamycin) being investigated.

Purpose of the Study:

  • To investigate the effects of the Hsp90 inhibitor 17-AAG on canine osteosarcoma cell lines.
  • To elucidate the interplay between apoptosis, autophagy, and mitophagy in response to 17-AAG treatment in different canine osteosarcoma cell types.

Main Methods:

  • Two canine osteosarcoma cell lines (D22 and D17) were treated with varying concentrations of 17-AAG (0.5 μM, 1 μM) for 24 and 48 hours.
  • Apoptosis, necrosis, autophagy, and mitophagy were assessed using transmission electron microscopy, flow cytometry, and immunofluorescence.

Main Results:

  • The D22 cell line (primary tumor origin) exhibited a simultaneous increase in apoptosis, autophagy, and mitophagy following 17-AAG treatment.
  • The D17 cell line (metastatic tumor origin) displayed significantly lower levels of apoptotic cell death compared to D22 cells.
  • These findings indicate differential cellular responses to drug-induced stress based on the specific tumor cell type.

Conclusions:

  • Tumor cell type significantly influences the response to Hsp90 inhibition and associated cell death pathways.
  • Pharmacological strategies combining proapoptotic chemotherapy with autophagy regulators may require predictive in vitro screening for optimal efficacy in canine osteosarcoma.
Keywords:
17-AAGapoptosisautophagycell deathcell linedoggeldanamycinmitophagyosteosarcomatanespimycin

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