Icaritin Inhibits JAK/STAT3 Signaling and Growth of Renal Cell Carcinoma

Abstract

Signal transducer and activator of transcription-3 (STAT3) is critical for cancer progression by regulating tumor cell survival, proliferation, and angiogenesis. Herein, we investigated the regulation of STAT3 activation and the therapeutic effects of Icaritin, a prenyl flavonoid derivative from Epimedium Genus, in renal cell carcinoma (RCC). Icaritin showed significant anti-tumor activity in the human and mouse RCC cell lines, 786-O and Renca, respectively. Icaritin inhibited both constitutive and IL-6-induced phospho-STAT3 (STAT3(Y705)) and reduced the level of STAT3-regulated proteins Bcl-xL, Mcl-1, Survivin, and CyclinD1 in a dose-dependent manner. Icaritin also inhibited activation of Janus-activated kinase-2 (JAK2), while it showed minimal effects on the activation of other key signaling pathways, including AKT and MAPK. Expression of the constitutively active form of STAT3 blocked Icaritin-induced apoptosis, while siRNA directed against STAT3 potentiated apoptosis. Finally, Icaritin significantly blunted RCC tumor growth in vivo, reduced STAT3 activation, and inhibited Bcl-xL and Cyclin E, as well as VEGF expression in tumors, which was associated with reduced tumor angiogenesis. Overall, these results suggest that Icaritin strongly inhibits STAT3 activation and is a potentially effective therapeutic option for the treatment of renal cell carcinoma.

DOI: 10.1371/journal.pone.0081657

Extracted Key Phrases

5 Figures and Tables

02004002014201520162017
Citations per Year

373 Citations

Semantic Scholar estimates that this publication has 373 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@inproceedings{Li2013IcaritinIJ, title={Icaritin Inhibits JAK/STAT3 Signaling and Growth of Renal Cell Carcinoma}, author={Shasha Li and Saul J. Priceman and Hong Xin and Wang Zhang and Jiehui Deng and Yong Liu and Jiabin Huang and Wenshan Zhu and Mingjie Chen and Wei Hu and Xiaomin Deng and Jian Zhang and Hua Yu and Guangyuan He}, booktitle={PloS one}, year={2013} }