Tumor recurrence is still a major challenge for clinical treatment of bladder cancer. Cumulative evidences indicate cancer stem cells (CSCs) contribute to drug resistance and leave a putative source for disease relapse. Identifying novel agents targeting CSCs may represent a new paradigm in the therapy of bladder cancer. Here, we separated a novel hedgehog (Hh) inhibitor, iG2, from streptomyces roseofulvus, which dramatically blocked the activation of Gli2 in bladder cancer cells. The iG2 strongly repressed the growth of cancer cells rather than the peri-tumor stroma cells. Attenuated proliferation and enhanced apoptosis of tumor cells were observed upon iG2 stimulation. Furthermore, iG2 reduced the self-renewal ability of bladder CSCs as well as the tumor formation. Collectively, iG2 is potentially used as a novel therapeutic agent for bladder cancer by targeting self-renewal through inhibiting Hh pathway.
Cancer medicine. 2016 Jul 27 [Epub ahead of print]
Lihong Zhu, Chen Ni, Baijun Dong, Yong Zhang, Yuefeng Shi, Haitao Niu, Chong Li
Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China., Medical Research Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China., Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China., Department of Urology, the Affiliated Hospital of Qingdao University, Qingdao, 266003, China., Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China., Department of Urology, the Affiliated Hospital of Qingdao University, Qingdao, 266003, China., Laboratory Animal Center, CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.