Article of the week: Modulating autophagy of prostate cancer cells with anti-androgen bicalutamide
Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.
In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.
Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video of Prof Leung and Dr Stockley discussing their paper.
If you only have time to read one article this week, it should be this one.
Does androgen-ablation therapy (AAT) associated autophagy have a pro-survival effect in LNCaP human prostate cancer cells?
Haley L. Bennett, Jacqueline Stockley†, Janis T. Fleming, Ranadip Mandal, Jim O’Prey*, Kevin M. Ryan*, Craig N. Robson† and Hing Y. Leung
Urology Research Laboratory and *Tumour Cell Death Research Laboratory, Beatson Institute for Cancer Research, Glasgow, and †Solid Tumour Target Discovery Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
OBJECTIVE
• 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.
MATERIALS AND METHODS
• LNCaP cells were treated with bicalutamide docetaxel, and cellular effects were assayed: lipidated LC3 (a microtubule-associated protein) for autophagy and its traffcking to fuse with lysosome; flow cytometry using propidium iodide or caspase 3 for cell death; and sulforhodamine B assay for cell growth.
RESULTS
• Bicalutamide treatment enhanced autophagy in LNCaP cells with increased level of autophagosome coupled with an altered cellular morphology reminiscent of neuroendocrine differentiation.
• Consistent with the literature on the interaction between androgen receptor activation and taxane chemotherapy, bicalutamide diminished docetaxel mediated cytotoxicity.
• Significantly, pharmacological inhibition of autophagy with 3-methyladenine significantly enhanced the efficacy cell kill mediated by AAT docetaxel.
CONCLUSION
• 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
Stunning images!
Autophagy is as important as robotic surgery for urologists interested in Prostate cancer. You will be hearing this term more often in future.
Well worth the read.