Journal article
Paradoxical effects of the autophagy inhibitor 3-methyladenine on docetaxel-induced toxicity in PC-3 and LNCaP prostate cancer cells
Naunyn-Schmiedeberg's Archives of Pharmacology, Vol.388(7), pp.793-799
2015
PMID: 25708950
Abstract
Docetaxel was the first chemotherapeutic agent to increase survival time in patients with androgen-resistant prostate cancer. However, it provides only a modest increase in survival and is associated with significant toxicity. Therefore, there is an urgent need to identify potential adjunct therapies. Given the key role of autophagy in both tumour survival and chemoresistance, the impact of autophagy modulation on docetaxel toxicity was tested in vitro. PC-3 and LNCaP cells were pre-treated with the autophagy inhibitor 3-methyladenine (5 mM) and then exposed to various concentrations (0-100 mu M) of docetaxel. Cytoxic effects of docetaxel were measured using resazurin reduction to resorufin, whilst autophagy and apoptosis was measured using monodansylcadaverine, annexin V and caspase-3, respectively. Docetaxel produced significant toxicity in PC-3 cells but was not toxic to LNCaP cells. Pre-treatment with the autophagy inhibitor, 3-methyladenine (5 mM) significantly protected PC-3 cells against docetaxel-induced cytotoxicity, increased autophagosome formation and apoptosis measured using monodansylcadaverine, annexin V and caspase-3 fluorescence, respectively. In contrast, 3-methyladenine was toxic by itself in LNCaP cells and also increased autophagic vesicle formation and apoptosis but did not influence docetaxel toxicity in these cells. These paradoxical effects of 3-methyladenine were largely independent of reactive oxygen species production. We show here that modulation of autophagy may influence docetaxel-induced toxicity in prostate cancer cells and these effects may differ between cell lines.
Details
- Title
- Paradoxical effects of the autophagy inhibitor 3-methyladenine on docetaxel-induced toxicity in PC-3 and LNCaP prostate cancer cells
- Authors
- Rebecca D. Pickard (Author) - Griffith UniversityBriohny H. Spencer (Author) - Griffith UniversityAmelia J. McFarland (Author) - Griffith UniversityNijole Bernaitis (Author) - Griffith UniversityAndrew K. Davey (Author) - Griffith UniversityAnthony V. Perkins (Author) - Griffith UniversityRuss Chess-Williams (Author) - Bond UniversityCatherine M. McDermott (Author) - Bond UniversityAmanda Forbes (Author) - Bond UniversityDavid Christie (Author) - Genesis CancerCareShailendra Anoopkumar-Dukie (Author) - Griffith University
- Publication details
- Naunyn-Schmiedeberg's Archives of Pharmacology, Vol.388(7), pp.793-799
- Publisher
- Springer
- DOI
- 10.1007/s00210-015-1104-7
- ISSN
- 1432-1912
- PMID
- 25708950
- Organisation Unit
- School of Health and Behavioural Sciences - Legacy; School of Health
- Language
- English
- Record Identifier
- 99685296902621
- Output Type
- Journal article
Metrics
21 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- Web Of Science research areas
- Pharmacology & Pharmacy
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites