Video: Androgen-ablation therapy (AAT) associated autophagy

 

 

 

 

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 trafficking 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.