Icaritin suppresses development of neuroendocrine differentiation of prostate cancer through inhibition of IL-6/STAT3 and Aurora kinase A pathways in TRAMP mice

In this study, we examined the mechanistic effects of a natural prenylflavonoid, icaritin (ICT), on neuroendocrine differentiation in IL-6-induced LNCaP cells and NEPC development in the male transgenic adenocarcinoma of the mouse prostate (TRAMP) model. TRAMP mice received daily intraperitoneal injection of ICT or vehicle. ICT induced apoptosis in prostate tumor, suppressed NEPC development and, accordingly, improved overall survival in TRAMP mice. Expression of neuroendocrine markers (synaptophysin) and androgen receptor in TRAMP mice and neuroendocrine-like LNCaP cells were inhibited by ICT. Suppression of neuroendocrine and NEPC development by ICT was associated with dose-dependent inhibitory effects on abnormally elevated IL-6/STAT3 and Aurora kinase A in vitro and in vivo. Since ICT demonstrated favorable pharmacokinetic and safety profiles with marked enrichment in prostate tissues, our study provides evidence for the development of prenylflavonoid as a multimodal therapeutic agent against NEPC.

Source: Carcinogenesis - July 6, 2016 Category: Cancer & Oncology Authors: Sun, F., Zhang, Z. W., Tan, E. M., Lim, Z. L. R., Li, Y., Wang, X. C., Chua, S. E., Li, J., Cheung, E., Yong, E.-L. Tags: Original Manuscript Source Type: research