Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis
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Qing Zhang1,*, Wei Zhao2,*, Changxiao Ye1,*, Junlong Zhuang1,*, Cunjie Chang2, Yuying Li3, Xiaojing Huang2, Lan Shen2, Yan Li3, Yangyan Cui2, Jiannan Song1, Bing Shen4, Isaac Eliaz5, Ruimin Huang6, Hao Ying3, Hongqian Guo1 and Jun Yan2
1 Department of Urology, Drum Tower Hospital, Medical School of Nanjing University; Institute of Urology, Nanjing University, Nanjing, Jiangsu, China
2 State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, Jiangsu, China
3 Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
4 Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China
5 Amitabha Medical Clinic and Healing Center, Santa Rosa, CA, USA
6 SIBS (Institute of Health Sciences)-Changhai Hospital Joint Center for Translational Research, Institutes for Translational Research (CAS-SMMU), Shanghai, China
* These authors have equally contributed to this study
Jun Yan, email:
Keywords: honokiol, bladder cancer, EZH2, microRNA
Received: March 22, 2015 Accepted: September 26, 2015 Published: October 15, 2015
The oncoprotein EZH2, as a histone H3K27 methyltransferase, is frequently overexpressed in various cancer types. However, the mechanisms underlying its role in urinary bladder cancer (UBC) cells have not yet fully understood. Herein, we reported that honokiol, a biologically active biphenolic compound isolated from the Magnolia officinalis inhibited human UBC cell proliferation, survival, cancer stemness, migration, and invasion, through downregulation of EZH2 expression level, along with the reductions of MMP9, CD44, Sox2 and the induction of tumor suppressor miR-143. Either EZH2 overexpression or miR-143 inhibition could partially reverse honokiol-induced cell growth arrest and impaired clonogenicity. Importantly, it was first revealed that EZH2 could directly bind to the transcriptional regulatory region of miR-143 and repress its expression. Furthermore, honokiol treatment on T24 tumor xenografts confirmed its anticancer effects in vivo, including suppression tumor growth and tumor stemness, accompanied by the dysregulation of EZH2 and miR-143 expressions. Our data suggest a promising therapeutic option to develop drugs targeting EZH2/miR-143 axis, such as honokiol, for bladder cancer treatment.
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