title: Synergistic anticancer activity of Thiazolo[5,4-b]quinoline derivative D3CLP in combination with cisplatin in human cervical cancer cells.
abstract: BACKGROUND
  D3CLP (9-[(3-chloro)phenylamine]-2-[3-(diethylamine)propylamine]thiazolo[5,4-b]quinoline) is a potent cytotoxic thiazolo[5,4-b]quinoline synthetic derivative that induces apoptosis of leukemia cells, while it displays low toxicity towards non-tumoral cells. The aim of this study was to determine if D3CLP can enhance the cytotoxicity of other antineoplastic drugs.
  
  
  METHODS
  Leukemia, breast and cervical cancer cell lines were exposed to D3CLP-alone or in combination with imatinib, tamoxifen or cisplatin, respectively. Cell viability after treatment was evaluated by the MTT assay, and cell death by the TUNEL assay. The effects of combined treatments were analyzed by combination index and isobolographic analysis.
  
  
  RESULTS
  Antiproliferative activity results indicate that D3CLP in combination with antineoplastic drugs induced a synergistic effect, at 3:1 and 1:1 ratios for D3CLP plus imatinib in K-562 leukemia cells, and at a 3:1 ratio for D3CLP with cisplatin in HeLa cells, as determined by their combination index. Furthermore, isobolographic analysis demonstrated a significant synergism for a 3:1 combination ratio of D3CLP with cisplatin in HeLa cells. In addition, TUNEL assay suggests cell death by apoptosis of HeLa cells after treatment with D3CLP and its combination with cisplatin at a 3:1 ratio.
  
  
  CONCLUSIONS
  Overall the results indicate that D3CLP, in combined preparation with antineoplastic drugs, is a good candidate for pre-clinical studies in the treatment of different carcinoma cell types.
authors.affiliation: Departament of Biology, Faculty of Chemistry. National Autonomous University of Mexico, Mexico D.F., 04510, Mexico.
authors.forename: Ignacio
authors.initials: I
authors.lastname: González-Sánchez
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lira-Rocha
authors.forename: Andrés
authors.initials: A
authors.lastname: Navarrete
authors.forename: Marco A
authors.initials: MA
authors.lastname: Loza-Mejía
authors.forename: Cristina
authors.initials: C
authors.lastname: Coronel-Cruz
authors.forename: C Adriana
authors.initials: CA
authors.lastname: Mendoza-Rodríguez
authors.forename: Marco A
authors.initials: MA
authors.lastname: Cerbón
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001549:Benzamides; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D061986:MCF-7 Cells; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: C560931:9-((3-chloro)phenylamine)-2-(3-(diethylamine)propylamine)thiazolo(5,4-b)quinoline; D000634:Aminoquinolines; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D013629:Tamoxifen; D000068877:Imatinib Mesylate; D002945:Cisplatin