Original triazine inductor of new specific molecular targets, with antitumor activity against nonsmall cell lung cancer

Abstract

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.

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1

“…There also remains a pressing need to develop strategies that target tumor cells and their genetic features [18]. In this study, our goal was to evaluate the effects of miR-183 on proliferation, EMT, migration and invasion of human NSCLC cells by its regulation of the expression of MTA1.…”

A novel large regulator RNA, B2, partially overlaps the HEF1/NEDD9/Cas-L gene

“…The HEF1 gene is known for its involvement in the control of cell growth, in apoptosis and in cell motility through its interaction with cellular adhesion sites and the mitotic spindle (5,19 (20). The C-terminal region of this p28 HEF1 seems to be responsible for the pro-apoptotic activity of HEF1.…”

“…In this approach, our aim was to demonstrate that HEF1 and B2 are involved in halting proliferation by inducing apoptosis in the anticancer chemotherapy of lung cancer. The work of Moreau et al (20) has highlighted the antitumour effect of the cytostatic molecule A190 on nude mice xenografted by non-small cell lung carcinomas.…”

Synthesis and cytotoxicity studies of bifunctional hybrids of nitrogen mustards with potential enzymes inhibitors based on melamine framework

“…Considering enzyme inhibition as an intrinsic property of the complete melamine structure, still remains vast potential of decoration of triazine scaffold by introducing "address" fragment increasing selectivity, components facilitating transport through the cell membranes, and last but not least, components of classic anticancer drugs with well-documented therapeutic competence. Therefore recent approaches involve development of hybrid cancer drugs 18 or application of 1,3,5-triazine as inductor of new specific molecular targets 19 . In these studies it has been attempted to introduce into 1,3,5-triazine scaffold one, two or three fragments bearing 2-chloroethylamine moiety characteristic for nitrogen mustards 20,21 and to confirm anti-proliferative activity of the obtained hybrids.…”