17-AAG and apoptosis, autophagy, and mitophagy in canine osteosarcoma cell lines

Massimini, M., Palmieri, C., De Maria, R., Romanucci, M., Malatesta, D., De Martinis, M., Maniscalco, L., Ciccarelli, A., Ginaldi, L., Buracco, P., Bongiovanni, L. and Della Salda, L. (2017) 17-AAG and apoptosis, autophagy, and mitophagy in canine osteosarcoma cell lines. Veterinary Pathology, 54 3: 405-412. doi:10.1177/0300985816681409


Author Massimini, M.
Palmieri, C.
De Maria, R.
Romanucci, M.
Malatesta, D.
De Martinis, M.
Maniscalco, L.
Ciccarelli, A.
Ginaldi, L.
Buracco, P.
Bongiovanni, L.
Della Salda, L.
Title 17-AAG and apoptosis, autophagy, and mitophagy in canine osteosarcoma cell lines
Journal name Veterinary Pathology   Check publisher's open access policy
ISSN 0300-9858
1544-2217
Publication date 2017-05-01
Year available 2017
Sub-type Article (original research)
DOI 10.1177/0300985816681409
Open Access Status Not yet assessed
Volume 54
Issue 3
Start page 405
End page 412
Total pages 8
Place of publication Thousand Oaks, CA United States
Publisher Sage Publications
Language eng
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 2 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 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 μM, 1 μM) 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 in apoptosis, autophagy, and mitophagy was observed only in the D22 cell line, while D17 cells 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 proapoptotic chemotherapy in association with autophagy regulators would benefit from a predictive in vitro screening of the target cell type.
Keyword Autophagy
Mitophagy
Apoptosis
Cell death
17-Aag
Geldanamycin
Tanespimycin
Osteosarcoma
Dog
Cell line
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Veterinary Science Publications
 
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