title: Screening of alternative drugs to the tumor suppressor miR-375 in esophageal squamous cell carcinoma using the connectivity map.
abstract: OBJECTIVE
  The aim of this study was to identify alternative compounds to the tumor suppressor miR-375 using the connectivity map (CMAP) and to validate the antitumor effects of the identified drugs in esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  Gene profiling of miR-375-treated TE2 and T.Tn cells was applied in order to search the CMAP database. Among the compounds identified using the CMAP, we focused on 8 drugs [(-)-epigallocatechin-3-gallate, metformin, rosiglitazone among others], excluding 2 drugs among the top 10 compounds. We evaluated whether these compounds possess tumor-suppressive functions in ESCC.
  
  
  RESULTS
  A cytotoxicity assay showed that the sensitivity of TE2 and T.Tn cells treated with the 8 compounds was evaluated based on IC50 values of 42.9 µM to 3.8 mM. A cell cycle analysis revealed that the percentage of TE2 and T.Tn cells incubated with 6 compounds in the G0/G1 phase or the G2/M phase increased by approximately 40-80%. A TUNEL assay showed that the percentages of apoptotic cells treated with almost all compounds were significantly increased (p < 0.05) compared with the control cells.
  
  
  CONCLUSIONS
  The CMAP database is a useful tool for identifying compounds affecting the same molecular pathways, particularly products that are difficult to apply via practical approaches, such as microRNAs.
authors.affiliation: Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Isozaki
authors.forename: Isamu
authors.initials: I
authors.lastname: Hoshino
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Akutsu
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hanari
authors.forename: Mikito
authors.initials: M
authors.lastname: Mori
authors.forename: Takanori
authors.initials: T
authors.lastname: Nishimori
authors.forename: Kentaro
authors.initials: K
authors.lastname: Murakami
authors.forename: Naoki
authors.initials: N
authors.lastname: Akanuma
authors.forename: Takeshi
authors.initials: T
authors.lastname: Toyozumi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suito
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Takeshita
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Maruyama
authors.forename: Akane
authors.initials: A
authors.lastname: Suzuki
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Hisahiro
authors.initials: H
authors.lastname: Matsubara
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001566:Benzocaine / Q000494:pharmacology; D001625:Betazole / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D003603:Cytotoxins / Q000494:pharmacology*; D017931:DNA Primers; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008687:Metformin / Q000494:pharmacology; D035683:MicroRNAs / Q000187:drug effects* / Q000378:metabolism; D016567:Nizatidine / Q000494:pharmacology; D010755:Organophosphates / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D040081:Protein Array Analysis; D060888:Real-Time Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D059467:Transcriptome; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000187:drug effects* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D017931:DNA Primers; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D010755:Organophosphates; D045162:Thiazolidinediones; D025521:Tumor Suppressor Proteins; D000077154:Rosiglitazone; D002635:Chenodeoxycholic Acid; C000380:fosfosal; D001625:Betazole; D002392:Catechin; D008687:Metformin; D011392:Proline; C045651:epigallocatechin gallate; D016567:Nizatidine; C003342:stachydrine; D001566:Benzocaine