title: Ridaifen G, tamoxifen analog, is a potent anticancer drug working through a combinatorial association with multiple cellular factors.
abstract: Ridaifen-G (RID-G), a tamoxifen analog that we previously synthesized, has potent growth inhibitory activity against various cancer cell lines. Tamoxifen is an anticancer drug known to act on an estrogen receptor (ER) and other proteins. However, our previous studies interestingly suggested that the mechanism of action of RID-G was different from that of tamoxifen. In order to investigate the molecular mode of action of RID-G, we developed a novel chemical genetic approach that combined a phage display screen with a statistical analysis of drug potency and gene expression profiles in thirty-nine cancer cell lines. Application of this method to RID-G revealed that three proteins, calmodulin (CaM), heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP A2/B1), and zinc finger protein 638 (ZNF638) were the candidates of direct targets of RID-G. Moreover, cell lines susceptible to RID-G show similar expression profiles of RID-G target genes. These results suggest that RID-G involves CaM, hnRNP A2/B1, and ZNF638 in its growth inhibitory activity.
authors: Department of Applied Biological Science, Tokyo University of Science, Chiba, Japan.
authors: Kentaro
authors: K
authors: Ikeda
authors: Department of Applied Biological Science, Tokyo University of Science, Chiba, Japan.
authors: Shinji
authors: S
authors: Kamisuki
authors: Department of Applied Chemistry, Tokyo University of Science, Tokyo, Japan.
authors: Shoko
authors: S
authors: Uetake
authors: Department of Applied Chemistry, Tokyo University of Science, Tokyo, Japan.
authors: Akihito
authors: A
authors: Mizusawa
authors: Department of Applied Chemistry, Tokyo University of Science, Tokyo, Japan.
authors: Nozomi
authors: N
authors: Ota
authors: Department of Applied Biological Science, Tokyo University of Science, Chiba, Japan.
authors: Tatsuki
authors: T
authors: Sasaki
authors: Department of Applied Biological Science, Tokyo University of Science, Chiba, Japan.
authors: Senko
authors: S
authors: Tsukuda
authors: Department of Applied Biological Science, Tokyo University of Science, Chiba, Japan.
authors: Tomoe
authors: T
authors: Kusayanagi
authors: Department of Applied Biological Science, Tokyo University of Science, Chiba, Japan.
authors: Yoichi
authors: Y
authors: Takakusagi
authors: Department of Molecular Genetics, The Ohio State University, Columbus, OH, United States.
authors: Kengo
authors: K
authors: Morohashi
authors: Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors: Takao
authors: T
authors: Yamori
authors: Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors: Shingo
authors: S
authors: Dan
authors: Department of Applied Chemistry, Tokyo University of Science, Tokyo, Japan.
authors: Isamu
authors: I
authors: Shiina
authors: Department of Applied Biological Science, Tokyo University of Science, Chiba, Japan. Electronic address: sugawara@rs.noda.tus.ac.jp.
authors: Fumio
authors: F
authors: Sugawara
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018408:Patch-Clamp Techniques; D019151:Peptide Library; D010766:Phosphorylation; D011485:Protein Binding; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors; D059467:Transcriptome / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002147:Calmodulin; D004268:DNA-Binding Proteins; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D009687:Nuclear Proteins; D019151:Peptide Library; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C099656:ZNF638 protein, human; C000608205:ridaifen G; D013629:Tamoxifen; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Anticancer drug; Phage display; Tamoxifen; Target identification