Canine osteosarcoma is highly resistant to current chemotherapy, thus clarifying the mechanisms of tumor cell resistance to treatments is an urgent need. We tested the Geldanamycin derivative 17-AAG (17-allylamino-17-demethoxygeldanamycin) - prototype of Hsp90 (Heat Shock Protein 90) inhibitors in two canine osteosarcoma cell lines, D22 and D17, derived from primary and metastatic tumors, respectively. With the aim to understand the interplay between cell death, autophagy and mitophagy, in the light of the dual effect of autophagy in regulating cancer cell viability and death, D22 and D17 cells were treated with different concentrations of 17-AAG (0.5 0M, 1 0M) for 24 and 48 hours. 17-AAG-induced apoptosis, necrosis, autophagy and mitophagy were assessed by transmission electron microscopy, flow cytometry and immunofluorescence. A simultaneous increase of apoptosis, autophagy and mitophagy was only observed in D22 cell line, while D17 cells only showed low levels of apoptotic cell death. These results reveal differential cell response to drug-induced stress depending on tumor cell type. Therefore, pharmacological treatments based on pro-apoptotic chemotherapy in association with autophagy regulators would benefit from a predictive in vitro screening of the target cell type.

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

DE MARTINIS, MASSIMO MARIA MARCELLO;GINALDI, Lia;
2017-01-01

Abstract

Canine osteosarcoma is highly resistant to current chemotherapy, thus clarifying the mechanisms of tumor cell resistance to treatments is an urgent need. We tested the Geldanamycin derivative 17-AAG (17-allylamino-17-demethoxygeldanamycin) - prototype of Hsp90 (Heat Shock Protein 90) inhibitors in two canine osteosarcoma cell lines, D22 and D17, derived from primary and metastatic tumors, respectively. With the aim to understand the interplay between cell death, autophagy and mitophagy, in the light of the dual effect of autophagy in regulating cancer cell viability and death, D22 and D17 cells were treated with different concentrations of 17-AAG (0.5 0M, 1 0M) for 24 and 48 hours. 17-AAG-induced apoptosis, necrosis, autophagy and mitophagy were assessed by transmission electron microscopy, flow cytometry and immunofluorescence. A simultaneous increase of apoptosis, autophagy and mitophagy was only observed in D22 cell line, while D17 cells only showed low levels of apoptotic cell death. These results reveal differential cell response to drug-induced stress depending on tumor cell type. Therefore, pharmacological treatments based on pro-apoptotic chemotherapy in association with autophagy regulators would benefit from a predictive in vitro screening of the target cell type.
File in questo prodotto:
File Dimensione Formato  
Veterinary Pathology 2016.pdf

accesso aperto

Tipologia: Documento in Post-print
Licenza: Creative commons
Dimensione 1.21 MB
Formato Adobe PDF
1.21 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11697/107659
Citazioni
  • ???jsp.display-item.citation.pmc??? 18
  • Scopus 31
  • ???jsp.display-item.citation.isi??? 31
social impact