Original triazine inductor of new specific molecular targets, with antitumor activity against nonsmall cell lung cancer.
Despite our growing insight into carcinogenesis, treatment of tumors, especially nonsmall cell lung cancer (NSCLC), remains limited and it is urgent to develop strategies that target tumor cells and their genetic features. Drug discovery efforts have historically focused on the search for compounds that modulate the protein products of genes. Current drug therapy targets only a few hundred endogenous targets, mainly proteins, such as receptors and enzymes. But now, the interest in specifically targeting RNA is increasing, both for target validation and/or therapeutic purposes. In this regard, our work was concerned with the induction of new molecular targets correlated to a cytostatic effect on NSCLC cell line, after treatment with a new triazin named A190. The in vitro study of cell cycle and apoptosis induction demonstrated the antiproliferative potential of this new compounds, and the use of quantitative RT-PCR analysis permit to display an original mechanism of action involving 2 genes: HEF1 and B2. The antitumor effect was also confirmed by the good results in vivo on nude mice xenografts.
Moreau
Dimitri
D
Laboratoire de Pharmacologie Marine, ISOMer, Faculté de Pharmacie de Nantes, 1 rue Gaston Veil, BP 92208, Nantes Cedex 03, France. dvmoreau@imcb.a-star.edu.sg
Jacquot
Catherine
C
Tsita
Polyxeni
P
Chinou
Ioanna
I
Tomasoni
Cristophe
C
Juge
Marcel
M
Antoniadou-Vyza
Ekaterini
E
Martignat
Lionel
L
Pineau
Alain
A
Roussakis
Christos
C
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000071183:Autophagy-Related Proteins; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D010750:Phosphoproteins / Q000378:metabolism; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
C532394:4,6-diamino-1,2-dihydro-1-(4''-chlorophenyl)-2-(1-tricyclo(3.3.1.1(3,4)) decyl-1,3,5-triazine); D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D000071183:Autophagy-Related Proteins; D008562:Membrane Glycoproteins; C099942:NEDD9 protein, human; C476215:PLEKHM1 protein, human; D010750:Phosphoproteins; D014227:Triazines