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 journalArticle

14 Citations (Scopus)

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

Fingerprint

Tumor Cell Line
Topoisomerase Inhibitors
Cell Line
Fluorouracil
Cell Proliferation
Organic Chemistry
Intercalating Agents
1,3-butadiene
1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene
Type I DNA Topoisomerase
Alkylating Agents
DNA
Paclitaxel
Platinum
Pharmaceutical Preparations
Doxorubicin
Nucleic Acids
Cisplatin
Inhibitory Concentration 50
Research

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

In: Oncology Reports, Vol. 12, No. 1, 07.2004, p. 91-96.

Research output: Contribution to journalArticle

Novi, Marino ; Ottone, Massimo ; Dell'Erba, Carlo ; Barbieri, Federica ; Chiavarina, Barbara ; Maccagno, Massimo ; Viale, Maurizio. / 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. In: Oncology Reports. 2004 ; Vol. 12, No. 1. pp. 91-96.
@article{cab43e54c5164f989d098a1ec35fc25d,
title = "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",
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.",
keywords = "1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene, Drug resistance, Mechanisms of resistance",
author = "Marino Novi and Massimo Ottone and Carlo Dell'Erba and Federica Barbieri and Barbara Chiavarina and Massimo Maccagno and Maurizio Viale",
year = "2004",
month = "7",
language = "English",
volume = "12",
pages = "91--96",
journal = "Oncology Reports",
issn = "1021-335X",
publisher = "Spandidos Publications",
number = "1",

}

TY - JOUR

T1 - 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

AU - Novi, Marino

AU - Ottone, Massimo

AU - Dell'Erba, Carlo

AU - Barbieri, Federica

AU - Chiavarina, Barbara

AU - Maccagno, Massimo

AU - Viale, Maurizio

PY - 2004/7

Y1 - 2004/7

N2 - 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.

AB - 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.

KW - 1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene

KW - Drug resistance

KW - Mechanisms of resistance

UR - http://www.scopus.com/inward/record.url?scp=10244275837&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10244275837&partnerID=8YFLogxK

M3 - Article

VL - 12

SP - 91

EP - 96

JO - Oncology Reports

JF - Oncology Reports

SN - 1021-335X

IS - 1

ER -