The inhibition of SOS-responses and MDR by phenothiazine-metal complexes

János Nacsa, László Nagy, Derek Sharples, Anikó Hevér, Diana Szabó, I. Ocsovszki, Andreas Varga, Sigfrid König, J. Molnár

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The gene of multidrug resistance (mdr) is inducible by different environmental stresses (SOS gene). We tested the inhibitory action of some new metal complexes of phenothiazines on megacin encoding bacterial gene induced by mitomycin-C as an example of 'SOS induction' and on efflux pump of mouse lymphoma cells. The interaction of compounds to DNA was measured by thermal stability of DNA. It was found that metal co-ordination complexes of trifluoperazine (TFP) and chlorpromazine (CPZ) added before mitomycin administration have an inhibitory action on megacine induction. The TFP-V(IV) complex was effective at a lower concentration than TFP alone. The inhibitory effect of some metal coordinating complexes (TFP-Cu(II) and TFP-V(IV)) exceeded the action of TFP alone on efflux pumps. We propose that these compounds can form a complex with the regulatory protein or DNA resulting in the inhibition of SOS response and inhibit the mdr function by inactivating the P-glycoprotein as well.

Original languageEnglish
Pages (from-to)3093-3098
Number of pages6
JournalAnticancer Research
Volume18
Issue number4 C
Publication statusPublished - Jul 1998

Fingerprint

Trifluoperazine
Coordination Complexes
Mitomycin
Megacins
DNA
MDR Genes
Phenothiazines
Bacterial Genes
Chlorpromazine
Multiple Drug Resistance
P-Glycoprotein
phenothiazine
Lymphoma
Hot Temperature
Metals
Genes
Proteins

Keywords

  • Chlorpromazine
  • mdr
  • Metal complex
  • Mitomycin
  • Phenothiazine
  • SOS
  • Stress respons gene
  • Thermal stability of DNA
  • Trifluoperazine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nacsa, J., Nagy, L., Sharples, D., Hevér, A., Szabó, D., Ocsovszki, I., ... Molnár, J. (1998). The inhibition of SOS-responses and MDR by phenothiazine-metal complexes. Anticancer Research, 18(4 C), 3093-3098.

The inhibition of SOS-responses and MDR by phenothiazine-metal complexes. / Nacsa, János; Nagy, László; Sharples, Derek; Hevér, Anikó; Szabó, Diana; Ocsovszki, I.; Varga, Andreas; König, Sigfrid; Molnár, J.

In: Anticancer Research, Vol. 18, No. 4 C, 07.1998, p. 3093-3098.

Research output: Contribution to journalArticle

Nacsa, J, Nagy, L, Sharples, D, Hevér, A, Szabó, D, Ocsovszki, I, Varga, A, König, S & Molnár, J 1998, 'The inhibition of SOS-responses and MDR by phenothiazine-metal complexes', Anticancer Research, vol. 18, no. 4 C, pp. 3093-3098.
Nacsa J, Nagy L, Sharples D, Hevér A, Szabó D, Ocsovszki I et al. The inhibition of SOS-responses and MDR by phenothiazine-metal complexes. Anticancer Research. 1998 Jul;18(4 C):3093-3098.
Nacsa, János ; Nagy, László ; Sharples, Derek ; Hevér, Anikó ; Szabó, Diana ; Ocsovszki, I. ; Varga, Andreas ; König, Sigfrid ; Molnár, J. / The inhibition of SOS-responses and MDR by phenothiazine-metal complexes. In: Anticancer Research. 1998 ; Vol. 18, No. 4 C. pp. 3093-3098.
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