ABSTRACT
Despite new protocols, non-small cell bronchopulmonary cancers are still difficult to treat by current chemotherapeutic procedures. Thus, it is essential to define new treatment strategies and detect new therapeutic targets. In order to define these new targets, this study applied the "differential display" (DD) technique to the NSCLC-N6 cell line treated with VT1 [methyl-4-methoxy-3-(3-methyl-2-butanoyl)benzoate]. VT1 induces arrest of the NSCLC-N6 cell cycle in the G1-phase, followed by cell death. DD enabled us to detect seven overexpressed mRNAs during treatment, four of which corresponded to identified genes: aldehyde dehydrogenase 1, nuclear transcription factor Nrfl, junctional adhesion molecule, and amino-ketobutyrate ligase. An antisense strategy showed that amino-ketobutyrate ligase is involved in the proliferation arrest of NSCLC-N6 cells in the G1-phase after VT1 treatment.
Subject(s)
Acetyltransferases/genetics , Aldehyde Dehydrogenase/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Cell Adhesion Molecules/genetics , Cell Division/genetics , DNA-Binding Proteins/genetics , Isoenzymes/genetics , Lung Neoplasms/genetics , Trans-Activators/genetics , Aldehyde Dehydrogenase 1 Family , Base Sequence , Carcinoma, Non-Small-Cell Lung/pathology , Cell Cycle/genetics , DNA Primers , Gene Expression Profiling , Humans , Junctional Adhesion Molecules , Lung Neoplasms/pathology , Molecular Sequence Data , Nuclear Respiratory Factor 1 , Nuclear Respiratory Factors , Oligodeoxyribonucleotides/chemistry , Retinal Dehydrogenase , Tumor Cells, CulturedABSTRACT
It is now well known that treatment of tumors, especially non-small-cell lung cancer (NSCLC), remains limited and it is urgent to develop strategies that target tumor cells and their genetic features. In this regard, our work is about genetic modifications arising in an in vitro NSCLC cell line after treatment with a chemical substance, methyl 4-methoxy-3-(3-methyl-2-butenoyl) benzoate (VT1). First, we showed that VT1 induces arrest of proliferation by blocking cells in the G1 phase of the cell cycle. Second, we use "differential display" strategy to clarify the genetic mechanisms involved in this proliferation arrest. A novel mRNA, NY-CO-1 (New-York Colon 1), of unknown function showed up-regulated expression after treatment. Application of "antisense" strategy confirmed this novel mRNA induction was effectively linked to growth arrest. Therefore, these data provide new information about mechanisms participating in arrest of proliferation of tumor cells and open new ways of treatment to target tumor growth.
Subject(s)
Alkenes/pharmacology , Antigens, Neoplasm/genetics , Antineoplastic Agents/pharmacology , Benzoates/pharmacology , Carcinoma, Non-Small-Cell Lung/genetics , Gene Expression Regulation, Neoplastic/drug effects , Lung Neoplasms/genetics , Antigens, Neoplasm/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Cycle/drug effects , Cell Division/drug effects , Cell Size/drug effects , DNA-Binding Proteins/analysis , Gene Expression Profiling , Humans , Lung Neoplasms/pathology , Nucleocytoplasmic Transport Proteins , Oligonucleotides, Antisense/pharmacology , RNA, Messenger/metabolism , Replication Protein A , Tumor Cells, Cultured , Up-RegulationABSTRACT
An aqueous extract of the marine diatom Haslea ostrearia (Simonsen) was studied for its antiproliferative properties against human solid tumors: lung carcinoma (NSCLC-N6), kidney carcinoma (E39) and melanoma (M96). These types of carcinoma are particularly chemoresistant. The extract has a potent cytostatic effect in vitro on the three cell lines and blocks the NSCLC-N6 line in the G1/S phase of the cell cycle. Moreover, the extract strongly inhibits tumor growth of NSCLC-N6 bearing nude mice. These preliminary results indicate that the aqueous extract of Haslea ostrearia exhibits inhibitory effects both in vitro and in vivo against solid carcinoma lines, suggesting the presence of a new potent antitumor agent in the aqueous algal homogenate.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Diatoms/chemistry , Kidney Neoplasms/drug therapy , Lung Neoplasms/drug therapy , Melanoma/drug therapy , Animals , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Kidney Neoplasms/pathology , Lung Neoplasms/pathology , Melanoma/pathology , Mice , Neoplasm Transplantation , Transplantation, Heterologous , Tumor Cells, CulturedABSTRACT
An organic extract of the marine diatom Skeletonema costatum was studied in vitro for its effect on asynchronous cells of a human non-small-cell bronchoplumanory carcinoma line (NSCLC-N6). Cell growth appeared to be inhibited in the G1 phase of the cell cycle, and kinetic studies in pretreated cells showed that this growth arrest was irreversible. These events are related to a terminal maturation induction.
