1,4-Bis(1-naphthyl)-2,3-dinitro-1,3-butadiene a novel anticancer compound effective against tumor cell lines characterized by different mechanisms of resistance

Marino Novi, Massimo Ottone, Carlo Dell'Erba, Federica Barbieri, Barbara Chiavarina, Massimo Maccagno, Maurizio Viale

Research output: Contribution to journalArticlepeer-review

Abstract

The inhibition of cell proliferation by 1,4-bis (l-naphthyl)-2,3-dinitro-l, 3-butadiene (Naph-DNB) was evaluated in vitro against 4 cell lines (L1210/DDP, A2780/ DX3, HCT-8/FU7dR, A549-T12) selected for their resistance to cisplatin, doxorubicin, 5-fluorouracil and taxol, and their wild-type counterparts. Naph-DNB is a novel anti-cancer compound obtained years ago within a research project of Organic Chemistry aimed at synthesizing 2,3-dinitrobutadiene derivatives. Because of its chemical structure, Naph- DNB was suggested to interact with nucleic acids, in particular DNA, and the other cellular macromolecules. This hypothesis made us consider Naph-DNB as a candidate for studies concerning its antitumour activity. We used the MTT assay to test the inhibition of cell proliferation after incubation of the cell lines with Naph-DNB for 72 h. For comparison, resistant and wild-type cell lines were also tested against those anticancer drugs used in vitro for their selection. In these culture conditions Naph-DNB retained its inhibiting activity against all resistant cells with IC50 values similar to those obtained in corresponding wild-type cell lines. Moreover, Naph-DNB was twice as effective as 5-fluorouracil against wild-type HCT-8 cells. Our previous findings about the interaction of Naph-DNB with DNA through the formation of interstrand cross-links suggested a mechanism of action similar to that of platinum/alkylating agents or topoisomerase inhibitors (intercalating agents). Our present data obtained by the K-SDS precipitation assay in A2780 and A549 cells showed that Naph-DNB is not able to form a stable topoisomerase-DNA complex as is the case for topoisomerase inhibitors. In conclusion, our results indicate that Naph-DNB is able to overcome some of the classical mechanisms of resistance selected by some anticancer drugs mainly used in clinical setting.

Original languageEnglish
Pages (from-to)91-96
Number of pages6
JournalOncology Reports
Volume12
Issue number1
Publication statusPublished - Jul 2004

Keywords

  • 1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene
  • Drug resistance
  • Mechanisms of resistance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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