Effect of nontoxic heat shock protein 90 inhibitor peptide derivatives on reversal of MDR of tumor cells

Joseph Molnár, Helga Engi, Yvette Mándi, Csaba Somlai, Botond Penke, Andrea Szabó, Antal Orosz

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Novel heat shock protein 90 inhibitor peptide derivatives [D-Trp-Phe-D-Trp-Leu-AMB (1), p-HOPA-D-Trp-Phe-D-Trp-Leu-ψ(CH2NH)-Leu-NH2 (2), D-Trp-Phe-D-Trp-OH (3), Suc-D-Trp-Phe-D-Trp-Leu-AMB (4), D-Tyr-Phe-D-Trp-Leu-AMB (5), D-Arg-D-Trp-Phe-D-Trp-Leu-Leu-NH2 (6), Leu-ψ(CH2NH)-Leu-NH2×2HCl (7), Phe-Trp-Phe-Trp-Leu-Leu-NH2 (8), Tyr-Trp-Phe-Trp-Leu-Leu-NH2 (9) and Tyr-D-Trp-Phe-D-Trp-Leu-Leu-NH2 (10)] were synthetized, and their ability to reverse multidrug resistance (MDR) was studied. Peptide derivatives 1, 4 and 5, with D-Trp or D-Tyr residues in the N-terminal position caused a marked inhibition of MDR in cancer cells. These MDR inhibitor compounds and epirubicin were demonstrated to have additive and synergistic antiproliferative effects in checkerboard experiments on human MDR1 gene-transfected mouse lymphoma cells in vitro. It is suggested that the MDR reversal effects of these anticancer peptide derivatives, together with their antiproliferative effects on lung cancer cells, may open up new horizons in cancer chemotherapy.

Original languageEnglish
Pages (from-to)429-434
Number of pages6
JournalIn Vivo
Volume21
Issue number2
Publication statusPublished - Mar 2007

Fingerprint

tryptophan-leucine
HSP90 Heat-Shock Proteins
Multiple Drug Resistance
Tumors
Cells
Derivatives
Peptides
Neoplasms
Epirubicin
Chemotherapy
Genes
Lymphoma
Lung Neoplasms
Drug Therapy
Experiments

Keywords

  • Heat shock protein 90 inhibitor
  • MDR reversal

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of nontoxic heat shock protein 90 inhibitor peptide derivatives on reversal of MDR of tumor cells. / Molnár, Joseph; Engi, Helga; Mándi, Yvette; Somlai, Csaba; Penke, Botond; Szabó, Andrea; Orosz, Antal.

In: In Vivo, Vol. 21, No. 2, 03.2007, p. 429-434.

Research output: Contribution to journalArticle

@article{6d0d8863950d49b2928ff772ca3cc900,
title = "Effect of nontoxic heat shock protein 90 inhibitor peptide derivatives on reversal of MDR of tumor cells",
abstract = "Novel heat shock protein 90 inhibitor peptide derivatives [D-Trp-Phe-D-Trp-Leu-AMB (1), p-HOPA-D-Trp-Phe-D-Trp-Leu-ψ(CH2NH)-Leu-NH2 (2), D-Trp-Phe-D-Trp-OH (3), Suc-D-Trp-Phe-D-Trp-Leu-AMB (4), D-Tyr-Phe-D-Trp-Leu-AMB (5), D-Arg-D-Trp-Phe-D-Trp-Leu-Leu-NH2 (6), Leu-ψ(CH2NH)-Leu-NH2×2HCl (7), Phe-Trp-Phe-Trp-Leu-Leu-NH2 (8), Tyr-Trp-Phe-Trp-Leu-Leu-NH2 (9) and Tyr-D-Trp-Phe-D-Trp-Leu-Leu-NH2 (10)] were synthetized, and their ability to reverse multidrug resistance (MDR) was studied. Peptide derivatives 1, 4 and 5, with D-Trp or D-Tyr residues in the N-terminal position caused a marked inhibition of MDR in cancer cells. These MDR inhibitor compounds and epirubicin were demonstrated to have additive and synergistic antiproliferative effects in checkerboard experiments on human MDR1 gene-transfected mouse lymphoma cells in vitro. It is suggested that the MDR reversal effects of these anticancer peptide derivatives, together with their antiproliferative effects on lung cancer cells, may open up new horizons in cancer chemotherapy.",
keywords = "Heat shock protein 90 inhibitor, MDR reversal",
author = "Joseph Moln{\'a}r and Helga Engi and Yvette M{\'a}ndi and Csaba Somlai and Botond Penke and Andrea Szab{\'o} and Antal Orosz",
year = "2007",
month = "3",
language = "English",
volume = "21",
pages = "429--434",
journal = "In Vivo",
issn = "0258-851X",
publisher = "International Institute of Anticancer Research",
number = "2",

}

TY - JOUR

T1 - Effect of nontoxic heat shock protein 90 inhibitor peptide derivatives on reversal of MDR of tumor cells

AU - Molnár, Joseph

AU - Engi, Helga

AU - Mándi, Yvette

AU - Somlai, Csaba

AU - Penke, Botond

AU - Szabó, Andrea

AU - Orosz, Antal

PY - 2007/3

Y1 - 2007/3

N2 - Novel heat shock protein 90 inhibitor peptide derivatives [D-Trp-Phe-D-Trp-Leu-AMB (1), p-HOPA-D-Trp-Phe-D-Trp-Leu-ψ(CH2NH)-Leu-NH2 (2), D-Trp-Phe-D-Trp-OH (3), Suc-D-Trp-Phe-D-Trp-Leu-AMB (4), D-Tyr-Phe-D-Trp-Leu-AMB (5), D-Arg-D-Trp-Phe-D-Trp-Leu-Leu-NH2 (6), Leu-ψ(CH2NH)-Leu-NH2×2HCl (7), Phe-Trp-Phe-Trp-Leu-Leu-NH2 (8), Tyr-Trp-Phe-Trp-Leu-Leu-NH2 (9) and Tyr-D-Trp-Phe-D-Trp-Leu-Leu-NH2 (10)] were synthetized, and their ability to reverse multidrug resistance (MDR) was studied. Peptide derivatives 1, 4 and 5, with D-Trp or D-Tyr residues in the N-terminal position caused a marked inhibition of MDR in cancer cells. These MDR inhibitor compounds and epirubicin were demonstrated to have additive and synergistic antiproliferative effects in checkerboard experiments on human MDR1 gene-transfected mouse lymphoma cells in vitro. It is suggested that the MDR reversal effects of these anticancer peptide derivatives, together with their antiproliferative effects on lung cancer cells, may open up new horizons in cancer chemotherapy.

AB - Novel heat shock protein 90 inhibitor peptide derivatives [D-Trp-Phe-D-Trp-Leu-AMB (1), p-HOPA-D-Trp-Phe-D-Trp-Leu-ψ(CH2NH)-Leu-NH2 (2), D-Trp-Phe-D-Trp-OH (3), Suc-D-Trp-Phe-D-Trp-Leu-AMB (4), D-Tyr-Phe-D-Trp-Leu-AMB (5), D-Arg-D-Trp-Phe-D-Trp-Leu-Leu-NH2 (6), Leu-ψ(CH2NH)-Leu-NH2×2HCl (7), Phe-Trp-Phe-Trp-Leu-Leu-NH2 (8), Tyr-Trp-Phe-Trp-Leu-Leu-NH2 (9) and Tyr-D-Trp-Phe-D-Trp-Leu-Leu-NH2 (10)] were synthetized, and their ability to reverse multidrug resistance (MDR) was studied. Peptide derivatives 1, 4 and 5, with D-Trp or D-Tyr residues in the N-terminal position caused a marked inhibition of MDR in cancer cells. These MDR inhibitor compounds and epirubicin were demonstrated to have additive and synergistic antiproliferative effects in checkerboard experiments on human MDR1 gene-transfected mouse lymphoma cells in vitro. It is suggested that the MDR reversal effects of these anticancer peptide derivatives, together with their antiproliferative effects on lung cancer cells, may open up new horizons in cancer chemotherapy.

KW - Heat shock protein 90 inhibitor

KW - MDR reversal

UR - http://www.scopus.com/inward/record.url?scp=34047240307&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34047240307&partnerID=8YFLogxK

M3 - Article

VL - 21

SP - 429

EP - 434

JO - In Vivo

JF - In Vivo

SN - 0258-851X

IS - 2

ER -