Does androgen-ablation therapy (AAT) associated autophagy have a pro-survival effect in LNCaP human prostate cancer cells?

Bennett, H.L., Stockley, J., Fleming, J.T., Mandal, R., O'Prey, J., Ryan, K.M. , Robson, C.N. and Leung, H.Y. (2013) Does androgen-ablation therapy (AAT) associated autophagy have a pro-survival effect in LNCaP human prostate cancer cells? BJU International, 111(4), pp. 672-682. (doi:10.1111/j.1464-410X.2012.11409.x)

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Abstract

<p>Objective</p> <p> • To study the cellular effects of the anti-androgen bicalutamide on autophagy and its potential impact on response to androgen-ablation therapy (AAT) alone or combined with docetaxel chemotherapy in human prostate cancer LNCaP cells.</p> <p>Materials and Methods</p> <p> • LNCaP cells were treated with bicalutamide ± docetaxel, and cellular effects were assayed: lipidated LC3 (a microtubule-associated protein) for autophagy and its trafficking to fuse with lysosome; flow cytometry using propidium iodide or caspase 3 for cell death; and sulforhodamine B assay for cell growth.</p> <p>Results</p> <p>• Bicalutamide treatment enhanced autophagy in LNCaP cells with increased level of autophagosome coupled with an altered cellular morphology reminiscent of neuroendocrine differentiation.</p> <p>• Consistent with the literature on the interaction between androgen receptor activation and taxane chemotherapy, bicalutamide diminished docetaxel mediated cytotoxicity.</p> <p>• Significantly, pharmacological inhibition of autophagy with 3-methyladenine significantly enhanced the efficacy cell kill mediated by AAT ± docetaxel.</p> <p>Conclusion</p> <p>• Autophagy associated with bicalutamide treatment in LNCaP cells may have a pro-survival effect and strategy to modulate autophagy may have a potential therapeutic value</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Leung, Professor Hing and Fleming, Ms Janice and Ryan, Professor Kevin and O'Prey, Mr James and Stockley, Dr Jacqueline
Authors: Bennett, H.L., Stockley, J., Fleming, J.T., Mandal, R., O'Prey, J., Ryan, K.M., Robson, C.N., and Leung, H.Y.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:BJU International
Publisher:Wiley-Blackwell
ISSN:1464-4096
ISSN (Online):1464-410X

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