title: Stabilization of G-quadruplex DNA and inhibition of Bcl-2 expression by a pyridostatin analog.
abstract: The G-quadruplexes located in the P1 promoter of B-cell lymphoma-2 (Bcl-2) gene are implicated to regulate Bcl-2 expression. Here, we designed a new pyridostatin analog named PDF, which exhibited high specificity and stabilizing effect toward G-quadruplexes. The luciferase assay demonstrated that PDF could significantly suppress Bcl-2 transcriptional activation in human laryngeal squamous carcinoma cells (Hep-2) cells. Besides, PDF also induced cell apoptosis in vitro assays. These results provide an excellent G-quadruplex specific ligand as an efficient Bcl-2 inhibitor. These results also implicate that PDF may be a potential anticancer drug to head neck cancer.
authors.affiliation: Otolaryngology Department, China-Japan Friendship Hospital, Beijing 100029, PR China. Electronic address: fjfengyun@sohu.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Otolaryngology Department, China-Japan Friendship Hospital, Beijing 100029, PR China.
authors.forename: Dazhang
authors.initials: D
authors.lastname: Yang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Chen
authors.affiliation: Cardiology Department, China-Japan Friendship Hospital, Beijing 100029, PR China. Electronic address: chengwenli2013@163.com.
authors.forename: Wenli
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Wang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, PR China. Electronic address: hongxsun@iccas.ac.cn.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Sun
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, PR China. Electronic address: tangyl@iccas.ac.cn.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects*; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D007830:Larynx / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010848:Picolinic Acids / Q000737:chemistry* / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D010848:Picolinic Acids; D019253:Proto-Oncogene Proteins c-bcl-2; C567962:pyridostatin; D004247:DNA
keywords: Bcl-2 gene; G-quadruplex; P1 promoter; Pyridostatin analog; Transcription