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Preliminary evaluation in vitro of the inhibition of cell proliferation, cytotoxicity and induction of apoptosis by 1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene

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Abstract

The pattern of inhibition of cell proliferation and cytotoxicity in vitro by 1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene (Naph-DNB) was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and the trypan blue (TB) dye exclusion assays in nine murine and human cell lines of different histologic origin. In our culture conditions Naph-DNB showed a good inhibiting activity against all cell lines tested, with IC50s varying within a narrow micromolar range of concentrations (2.0 ± 0.2–14.3 ± 2.3 μM). In particular, murine P388 (leukemia), human Jurkat (leukemia), A2780, PA-1 (ovarian carcinoma) and Saos-2 (osteosarcoma) cells showed the highest sensitivity to the inhibiting potential of Naph-DNB, while human A549 (non small cell lung cancer, NSCLC), MDA-MB-231 (breast cancer), HGC-27 (gastric cancer) and HCT-8 (colon carcinoma) were the least sensitive cell lines. Moreover, the analysis of cytotoxicity of Naph-DNB evaluated by the TB test showed that this compound was able to kill cells with IC50s ranging from 1.7 to 39.2 μM. The study of the induction of apoptosis was carried out by 4′-6-diamidine-2′-phenylindole (DAPI) staining of segmented nuclei, western blot of p53 protein and TdT-mediated dUTP-biotin nick end labeling (TUNEL) method, while the interaction with DNA was evaluated through the analysis of interstrand cross-link (ISCL) formation.

Our data show that in all cell lines tested Naph-DNB was able to form ISCLs, to upregulate p53 oncosuppressor-protein and to induce apoptosis. Moreover, TUNEL analysis also suggested that Naph-DNB, similarly to other anticancer drugs, was able to block cells in the G 0/G 1 phase of the cell cycle.

In conclusion our data suggest that Naph-DNB may be an effective novel lead molecule for the design of new anticancer compounds.

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Authors and Affiliations

  1. S.C. di Farmacologia e Neuroscienze, Istituto Nazionale per la Ricerca sul Cancro, Lgo R. Benzi 10, 16132, Genova, Italy

    Maurizio Viale, Massimo Ottone & Barbara Chiavarina

  2. Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione di Patologia Generale e Oncologia Sperimentale, Università di Bari, Italy

    Maria A. Mariggiò & Angela Vinella

  3. Biofisica e Citometria, Istituto Nazionale per la Ricerca sul Cancro, Lgo R. Benzi 10, 16132, Genova, Italy

    Claudia Prevosto

  4. Dipartimento di Chimica e Chimica Industriale, Università di Genova, Via Dodecaneso 31, 16146, Genova, Italy

    Carlo Dell'Erba, Giovanni Petrillo & Marino Novi

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  1. Maurizio Viale
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  2. Maria A. Mariggiò
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  9. Marino Novi
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Viale, M., Mariggiò, M.A., Ottone, M. et al. Preliminary evaluation in vitro of the inhibition of cell proliferation, cytotoxicity and induction of apoptosis by 1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene. Invest New Drugs 22, 359–367 (2004). https://doi.org/10.1023/B:DRUG.0000036678.25436.3d

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  • DOI: https://doi.org/10.1023/B:DRUG.0000036678.25436.3d

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