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
• 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 trafficking to fuse with lysosome; ﬂow cytometry using propidium iodide or caspase 3 for cell death; and sulforhodamine B assay for cell growth.
• 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.
• Autophagy associated with bicalutamide treatment in LNCaP cells may have a pro-survival effect and strategy to modulate autophagy may have a potential therapeutic