title: A novel hedgehog inhibitor iG2 suppresses tumorigenesis by impairing self-renewal in human bladder cancer.
abstract: 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.
authors.affiliation: Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Medical Research Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Ni
authors.affiliation: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
authors.forename: Baijun
authors.initials: B
authors.lastname: Dong
authors.affiliation: Department of Urology, the Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China.
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Urology, the Affiliated Hospital of Qingdao University, Qingdao, 266003, China. niuht0532@126.com.
authors.forename: Haitao
authors.initials: H
authors.lastname: Niu
authors.affiliation: Laboratory Animal Center, CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. lichong@moon.ibp.ac.cn.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000066673:Cell Self Renewal / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism*; D004195:Disease Models, Animal; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D053823:Hedgehog Proteins
keywords: Bladder cancer; Gli2; hedgehog; iG2