title: Cucurbitacin-D-induced CDK1 mRNA up-regulation causes proliferation arrest of a non-small cell lung carcinoma cell line (NSCLC-N6).
abstract: Despite progress in chemotherapeutic agents, non-small cell lung cancers (NSCLC) still have a poor survival rate. Thus, development of new therapeutic strategies, specifically against cancer cells is still required. For this purpose, we treated the non-small cell lung cancer cell line NSCLC-N6 with the natural product cucurbitacin D (CucD) - extracted from the plant Ecballium elaterium in order first to assess its in vitro cytotoxicity, but also to study the genetic changes that it could bring out. CucD has shown a blocking in the G1 phase of the cell cycle in NSCLC-N6 cells prior to apoptotic cell death. The reverse transcriptase-polymerase chain reaction-differential display (RT-PCR-DD) technique was also applied on treated cells to elucidate the genetic mechanisms involved. We revealed an overexpression of Cyclin-dependent kinase 1 (CDK1) mRNA after treatment and, with the use of antisense oligonucleotides, an effective role in the proliferation arrest of NSCLC-N6 cells. The present study provides new insights about the mechanisms of proliferation arrest in tumor cells and open new ways of treatment to target tumor growth.
authors.affiliation: Equipe IICIMed EA 1155, Laboratoire CPCM, Faculté de Pharmacie, Université de Nantes, Nantes, France Catherine.jacquot@univ-nantes.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Jacquot
authors.affiliation: Equipe IICIMed EA 1155, Laboratoire CPCM, Faculté de Pharmacie, Université de Nantes, Nantes, France.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Rousseau
authors.affiliation: Equipe IICIMed EA 1155, Laboratoire CPCM, Faculté de Pharmacie, Université de Nantes, Nantes, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Carbonnelle
authors.affiliation: Division of Pharmacognosy and Chemistry of Natural Products, University of Athens, Athens, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Chinou
authors.affiliation: Equipe IICIMed EA 1155, Laboratoire CPCM, Faculté de Pharmacie, Université de Nantes, Nantes, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Malleter
authors.affiliation: Equipe IICIMed EA 1155, Laboratoire CPCM, Faculté de Pharmacie, Université de Nantes, Nantes, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Tomasoni
authors.affiliation: Equipe IICIMed EA 1155, Laboratoire CPCM, Faculté de Pharmacie, Université de Nantes, Nantes, France.
authors.forename: Christos
authors.initials: C
authors.lastname: Roussakis
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D016203:CDC2 Protein Kinase / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014315:Triterpenes / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D014315:Triterpenes; C038105:cucurbitacin D; D016203:CDC2 Protein Kinase
keywords: CDK1; Cucurbitacin D; Ecbalium elaterium; G1 cell cycle arrest; NSCLC-N6; apoptosis; gene expression; lung cancer