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Abstract

Volume 19, Issue 6 (November 2017) 19, 686–693; 10.4103/1008-682X.191518

Potential therapeutic effect of epigenetic therapy on treatment‑induced neuroendocrine prostate cancer

Xiang Xu1, 2, Yu-Hua Huang3, Yan-Jing Li2, Alexa Cohen2, Zhen Li4, Jill Squires2, Wei Zhang5, Xu-Feng Chen2, Min Zhang1, Jiao-Ti Huang2

1 School of Life Sciences, Anhui University, Hefei, China
2 Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, California, USA
3 Department of Urology, The First Affiliated Hospital of SooChow University, Suzhou, China
4 Department of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
5 Department of Pathology, Beijing Hospital, Beijing, China

Correspondence: Dr. JT Huang (jiaoti.huang@duke.edu) or Dr. M Zhang (zhmin07@163.com)

Date of Submission 30-Mar-2016 Date of Decision 21-Jun-2016 Date of Acceptance 07-Sep-2015 Date of Web Publication 29-Nov-2016

Abstract

Although adenocarcinomas of the prostate are relatively indolent, some patients with advanced adenocarcinomas show recurrence of treatment-induced neuroendocrine prostate cancer, which is highly aggressive and lethal. Detailed biological features of treatment-induced neuroendocrine prostate cancer have not been characterized owing to limited biopsies/resections and the lack of a cellular model. In this study, we used a unique cellular model (LNCaP/NE1.8) to investigate the potential role of cancer stem cells in treatment-induced neuroendocrine prostate cancer with acquired resistance to hormonal therapy and chemotherapy. We also studied the role of cancer stem cells in enhancing invasion in treatment-induced neuroendocrine prostate cancer cells that recurred after long-term androgen-ablation treatment. Using an in vitro system mimicking clinical androgen-ablation, our results showed that the neuroendocrine-like subclone NE1.8 cells were enriched with cancer stem cells. Compared to parental prostate adenocarcinoma LNCaP cells, NE1.8 cells are more resistant to androgen deprivation therapy and chemotherapeutic agents and show increased cancer cell invasiveness. Results from this study also suggest a potential epigenetic therapeutic strategy using suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, as a chemotherapeutic agent for therapy-resistant treatment-induced neuroendocrine prostate cancer cells to minimize the risk of prostate cancer recurrence and metastasis.

Keywords: cancer stem cell; epigenetic therapy; hormonal therapy; neuroendocrine prostate cancer; suberoylanilide hydroxamic acid

Keywords: cancer stem cell; epigenetic therapy; hormonal therapy; neuroendocrine prostate cancer; suberoylanilide hydroxamic acid

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