Effect of new thioacridine derivatives on P-gp function and on mdr1 gene expression

Aniko Hevér, Christiane Santelli-Rouvier, Pierre Brouant, Said El Khyari, J. Molnár, Yves Barra, Jacques Barbe

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

We studied the effect of thioacridine derivatives on the function of P-glycoprotein in MDR mouse T-lymphoma cell line L5178 and in MDR human leukemia cell line K562/ADR by rhodamine 123 uptake assay. The effect of some selected thioacridines was also investigated on the expression of the mdr1 gene. Expression was analysed by RT-PCR. Two compounds: 3-amino-9-thio-(4'-nitrobenzyl)acridinone and 2,7-dimethoxy-9-thio-(2'-diethlaminoethyl) acridinone were able to block the function of the P-gp, and also to decrease significantly mdr1 demonstrated gene expression. Because these two derivatives exert their positive simultaneously effects as reversing agents they could be potential candidate anticancer agents for further investigation. The thioacridines, which do not affect P-gp function, do not affect or increase the expression of mdr1 gene. Our results showed the structure-activity relationships of these compounds, providing a direction for the development of new, more active compounds.

Original languageEnglish
Pages (from-to)3053-3058
Number of pages6
JournalAnticancer Research
Volume18
Issue number4 C
Publication statusPublished - Jul 1998

Fingerprint

Gene Expression
Rhodamine 123
Cell Line
P-Glycoprotein
Structure-Activity Relationship
Antineoplastic Agents
Lymphoma
Leukemia
Polymerase Chain Reaction
Direction compound

Keywords

  • mdr1 gene
  • P-glycoprotein
  • Thioacridines

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hevér, A., Santelli-Rouvier, C., Brouant, P., El Khyari, S., Molnár, J., Barra, Y., & Barbe, J. (1998). Effect of new thioacridine derivatives on P-gp function and on mdr1 gene expression. Anticancer Research, 18(4 C), 3053-3058.

Effect of new thioacridine derivatives on P-gp function and on mdr1 gene expression. / Hevér, Aniko; Santelli-Rouvier, Christiane; Brouant, Pierre; El Khyari, Said; Molnár, J.; Barra, Yves; Barbe, Jacques.

In: Anticancer Research, Vol. 18, No. 4 C, 07.1998, p. 3053-3058.

Research output: Contribution to journalArticle

Hevér, A, Santelli-Rouvier, C, Brouant, P, El Khyari, S, Molnár, J, Barra, Y & Barbe, J 1998, 'Effect of new thioacridine derivatives on P-gp function and on mdr1 gene expression', Anticancer Research, vol. 18, no. 4 C, pp. 3053-3058.
Hevér A, Santelli-Rouvier C, Brouant P, El Khyari S, Molnár J, Barra Y et al. Effect of new thioacridine derivatives on P-gp function and on mdr1 gene expression. Anticancer Research. 1998 Jul;18(4 C):3053-3058.
Hevér, Aniko ; Santelli-Rouvier, Christiane ; Brouant, Pierre ; El Khyari, Said ; Molnár, J. ; Barra, Yves ; Barbe, Jacques. / Effect of new thioacridine derivatives on P-gp function and on mdr1 gene expression. In: Anticancer Research. 1998 ; Vol. 18, No. 4 C. pp. 3053-3058.
@article{0db707303fe14bbf84f5cbbf32f923b0,
title = "Effect of new thioacridine derivatives on P-gp function and on mdr1 gene expression",
abstract = "We studied the effect of thioacridine derivatives on the function of P-glycoprotein in MDR mouse T-lymphoma cell line L5178 and in MDR human leukemia cell line K562/ADR by rhodamine 123 uptake assay. The effect of some selected thioacridines was also investigated on the expression of the mdr1 gene. Expression was analysed by RT-PCR. Two compounds: 3-amino-9-thio-(4'-nitrobenzyl)acridinone and 2,7-dimethoxy-9-thio-(2'-diethlaminoethyl) acridinone were able to block the function of the P-gp, and also to decrease significantly mdr1 demonstrated gene expression. Because these two derivatives exert their positive simultaneously effects as reversing agents they could be potential candidate anticancer agents for further investigation. The thioacridines, which do not affect P-gp function, do not affect or increase the expression of mdr1 gene. Our results showed the structure-activity relationships of these compounds, providing a direction for the development of new, more active compounds.",
keywords = "mdr1 gene, P-glycoprotein, Thioacridines",
author = "Aniko Hev{\'e}r and Christiane Santelli-Rouvier and Pierre Brouant and {El Khyari}, Said and J. Moln{\'a}r and Yves Barra and Jacques Barbe",
year = "1998",
month = "7",
language = "English",
volume = "18",
pages = "3053--3058",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "4 C",

}

TY - JOUR

T1 - Effect of new thioacridine derivatives on P-gp function and on mdr1 gene expression

AU - Hevér, Aniko

AU - Santelli-Rouvier, Christiane

AU - Brouant, Pierre

AU - El Khyari, Said

AU - Molnár, J.

AU - Barra, Yves

AU - Barbe, Jacques

PY - 1998/7

Y1 - 1998/7

N2 - We studied the effect of thioacridine derivatives on the function of P-glycoprotein in MDR mouse T-lymphoma cell line L5178 and in MDR human leukemia cell line K562/ADR by rhodamine 123 uptake assay. The effect of some selected thioacridines was also investigated on the expression of the mdr1 gene. Expression was analysed by RT-PCR. Two compounds: 3-amino-9-thio-(4'-nitrobenzyl)acridinone and 2,7-dimethoxy-9-thio-(2'-diethlaminoethyl) acridinone were able to block the function of the P-gp, and also to decrease significantly mdr1 demonstrated gene expression. Because these two derivatives exert their positive simultaneously effects as reversing agents they could be potential candidate anticancer agents for further investigation. The thioacridines, which do not affect P-gp function, do not affect or increase the expression of mdr1 gene. Our results showed the structure-activity relationships of these compounds, providing a direction for the development of new, more active compounds.

AB - We studied the effect of thioacridine derivatives on the function of P-glycoprotein in MDR mouse T-lymphoma cell line L5178 and in MDR human leukemia cell line K562/ADR by rhodamine 123 uptake assay. The effect of some selected thioacridines was also investigated on the expression of the mdr1 gene. Expression was analysed by RT-PCR. Two compounds: 3-amino-9-thio-(4'-nitrobenzyl)acridinone and 2,7-dimethoxy-9-thio-(2'-diethlaminoethyl) acridinone were able to block the function of the P-gp, and also to decrease significantly mdr1 demonstrated gene expression. Because these two derivatives exert their positive simultaneously effects as reversing agents they could be potential candidate anticancer agents for further investigation. The thioacridines, which do not affect P-gp function, do not affect or increase the expression of mdr1 gene. Our results showed the structure-activity relationships of these compounds, providing a direction for the development of new, more active compounds.

KW - mdr1 gene

KW - P-glycoprotein

KW - Thioacridines

UR - http://www.scopus.com/inward/record.url?scp=0031813571&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031813571&partnerID=8YFLogxK

M3 - Article

C2 - 9713509

AN - SCOPUS:0031813571

VL - 18

SP - 3053

EP - 3058

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 4 C

ER -