Proliferation arrest in G1 phase of a non-small cell lung cancer cell line (NSCLC-N6) treated by an original compound methyl-4-methoxy-3-(3-methyl-2-butanoyl) benzoate (VT1) independently of the p53/p21 cascade.
Non-small cell lung cancers remain difficult to treat and have a high death rate and poor 5-year survival. New therapeutic strategies are urgently needed, which should be more specific for the cancer cell and less toxic for normal cells. In this respect, induction of the terminal differentiation of tumor cells appears to be a particularly suitable approach, which can only be achieved after proliferation arrest in G1 phase. This study describes the activity of a chemical compound with an original structure, namely methyl-4-methoxy-3-(3-methyl-2-butanoyl) benzoate (VT1), which induced irreversible proliferation arrest in G1 phase of two lung cancer lines, NSCLC-N6 and NSCLC-derived A549 cells. The p53 gene is now unanimously regarded as a key gene for cell cycle arrest in G1 phase, and A549 cells possess a wild-type p53 gene. The similarity of effects obtained on both lines led us to consider whether the p53/p21 cascade was activated in NSCLC-N6 cells during VT1 treatment. The mutational status of p53 gene was first established in the NSCLC-N6 line using a PCR SSCP technique, and a reporter gene was then used to assess the functionality of P53 protein.
Jacquot
Catherine
C
Laboratoire de Pharmacologie Marine (EE0103), Faculté de Pharmacie de Nantes, 44035 Nantes Cedex, France.
Moreau
Dimitri
D
Tomasoni
Christophe
C
Juge
Marcel
M
Coiffard
Laurence
L
Roussis
Vasilios
V
Roussakis
Christos
C
D000475:Alkenes / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D000475:Alkenes; D001565:Benzoates; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C423823:methyl-4-methoxy-3-(3-methyl-2-butenoyl) benzoate