Oncotarget

Research Papers:

Identification of sphingosine kinase 1 (SphK1) as a primary target of icaritin in hepatocellular carcinoma cells

Pei-Hua Lu, Min-Bin Chen, Yuan-Yuan Liu, Mian-Hua Wu, Wen-Ting Li, Mu-Xin Wei, Chao-Ying Liu and Shu-Kui Qin _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:22800-22810. https://doi.org/10.18632/oncotarget.15205

Metrics: PDF 2150 views  |   HTML 1560 views  |   ?  


Abstract

Pei-Hua Lu1,2,*, Min-Bin Chen3,*, Yuan-Yuan Liu3,*, Mian-Hua Wu2, Wen-Ting Li2, Mu-Xin Wei4, Chao-Ying Liu1, Shu-Kui Qin5

1Department of Medical Oncology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China

2Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor of Nanjing University of Chinese Medicine, Nanjing, China

3Department of Oncology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, China

4Department of Traditional Chinese Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, China

5People’s Liberation Army Cancer Center, 81st Hospital of People’s Liberation Army, Nanjing, China

*Co-first authors

Correspondence to:

Shu-Kui Qin, email: drqinshukuinj@126.com

Min-Bin Chen, email: cmb1981@163.com

Keywords: hepatocellular carcinoma (HCC), icaritin, sphingosine kinase 1 (SphK1), ceramide

Received: September 20, 2016     Accepted: November 08, 2016     Published: February 09, 2017

ABSTRACT

Hepatocellular carcinoma (HCC) is a highly aggressive neoplasm. We aim to explore the anti-HCC activity by a natural prenylflavonoid icaritin. Icaritin was cytotoxic and pro-apoptotic when added to established (HepG2, KYN-2 and Huh-7 lines) and primary human HCC cells. At the signaling level, icaritin inhibited sphingosine kinase 1 (SphK1) activity in HCC cells, which led to pro-apoptotic ceramide production and JNK1 activation. SphK1 inhibition or silence (by shRNA/microRNA) mimicked icaritin-mediated cytotoxicity, and almost nullified icaritin’s activity in HepG2 cells. Reversely, exogenous over-expression of SphK1 sensitized icaritin-induced HepG2 cell apoptosis. In vivo, oral administration of icaritin dramatically inhibited HepG2 xenograft growth in SCID mice. Further, SphK1 activity in icaritin-treated tumors was largely inhibited. In summary, icaritin exerts potent anti-HCC activity in vitro and in vivo. SphK1 inhibition could be the primary mechanism of its actions in HCC cells.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 15205