Effect of cyclosporin analogues and FK506 on transcellular transport of daunorubicin and vinblastine via P-glycoprotein

Kumiko Tanaka, Midori Hirai, Yusuke Tanigawara, Masato Yasuhara, Ryohei Hori, Kazumitsu Ueda, Ken Ichi Inui

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Purpose. P-glycoprotein-mediated transcellular transport of anticancer agents and the inhibitory effect of cyclosporin analogs and FK506 were investigated. Methods. The transcellular transport of daunorubicin and vinblastine by monolayers of LLC-GA5-COL150 cells which overexpressed P-glycoprotein was measured in the presence and absence of cyclosporins or FK506. Results. Cyclosporins and FK506 inhibited P-glycoprotein-mediated transport of daunorubicin and vinblastine in the order of cyclosporin D, dihydrocyclosporin D > cyclosporin A > FK506 > cyclosporin C, dihydrocyclosporin C. The intracellular accumulation of the anticancer agents was highly associated with the transporting function of P-glycoprotein. The inhibitory effect of cyclosporin D was concentration-dependent. The inhibitory effect of the modulators on P-glycoprotein was not correlated with the immunosuppressive activity, but was correlated with their lipophilicity. Conclusions. In the transcellular transport system, lipophilicity may be one of the determinants for the inhibitory effect of various multidrug resistance modulators on the P-glycoprotein-mediated transport.

Original languageEnglish
Pages (from-to)1073-1077
Number of pages5
JournalPharmaceutical Research
Volume13
Issue number7
DOIs
Publication statusPublished - 1996
Externally publishedYes

Fingerprint

Transcytosis
Daunorubicin
Vinblastine
P-Glycoprotein
Tacrolimus
Cyclosporine
Cyclosporins
Antineoplastic Agents
Modulators
Multiple Drug Resistance
Immunosuppressive Agents
Monolayers

Keywords

  • Cyclosporine
  • Daunorubicin
  • FK506
  • P-glycoprotein
  • Vinblastine

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

Effect of cyclosporin analogues and FK506 on transcellular transport of daunorubicin and vinblastine via P-glycoprotein. / Tanaka, Kumiko; Hirai, Midori; Tanigawara, Yusuke; Yasuhara, Masato; Hori, Ryohei; Ueda, Kazumitsu; Inui, Ken Ichi.

In: Pharmaceutical Research, Vol. 13, No. 7, 1996, p. 1073-1077.

Research output: Contribution to journalArticle

Tanaka, Kumiko ; Hirai, Midori ; Tanigawara, Yusuke ; Yasuhara, Masato ; Hori, Ryohei ; Ueda, Kazumitsu ; Inui, Ken Ichi. / Effect of cyclosporin analogues and FK506 on transcellular transport of daunorubicin and vinblastine via P-glycoprotein. In: Pharmaceutical Research. 1996 ; Vol. 13, No. 7. pp. 1073-1077.
@article{56b2fbf4fe3243a0bf9d297668b527bd,
title = "Effect of cyclosporin analogues and FK506 on transcellular transport of daunorubicin and vinblastine via P-glycoprotein",
abstract = "Purpose. P-glycoprotein-mediated transcellular transport of anticancer agents and the inhibitory effect of cyclosporin analogs and FK506 were investigated. Methods. The transcellular transport of daunorubicin and vinblastine by monolayers of LLC-GA5-COL150 cells which overexpressed P-glycoprotein was measured in the presence and absence of cyclosporins or FK506. Results. Cyclosporins and FK506 inhibited P-glycoprotein-mediated transport of daunorubicin and vinblastine in the order of cyclosporin D, dihydrocyclosporin D > cyclosporin A > FK506 > cyclosporin C, dihydrocyclosporin C. The intracellular accumulation of the anticancer agents was highly associated with the transporting function of P-glycoprotein. The inhibitory effect of cyclosporin D was concentration-dependent. The inhibitory effect of the modulators on P-glycoprotein was not correlated with the immunosuppressive activity, but was correlated with their lipophilicity. Conclusions. In the transcellular transport system, lipophilicity may be one of the determinants for the inhibitory effect of various multidrug resistance modulators on the P-glycoprotein-mediated transport.",
keywords = "Cyclosporine, Daunorubicin, FK506, P-glycoprotein, Vinblastine",
author = "Kumiko Tanaka and Midori Hirai and Yusuke Tanigawara and Masato Yasuhara and Ryohei Hori and Kazumitsu Ueda and Inui, {Ken Ichi}",
year = "1996",
doi = "10.1023/A:1016019010339",
language = "English",
volume = "13",
pages = "1073--1077",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "7",

}

TY - JOUR

T1 - Effect of cyclosporin analogues and FK506 on transcellular transport of daunorubicin and vinblastine via P-glycoprotein

AU - Tanaka, Kumiko

AU - Hirai, Midori

AU - Tanigawara, Yusuke

AU - Yasuhara, Masato

AU - Hori, Ryohei

AU - Ueda, Kazumitsu

AU - Inui, Ken Ichi

PY - 1996

Y1 - 1996

N2 - Purpose. P-glycoprotein-mediated transcellular transport of anticancer agents and the inhibitory effect of cyclosporin analogs and FK506 were investigated. Methods. The transcellular transport of daunorubicin and vinblastine by monolayers of LLC-GA5-COL150 cells which overexpressed P-glycoprotein was measured in the presence and absence of cyclosporins or FK506. Results. Cyclosporins and FK506 inhibited P-glycoprotein-mediated transport of daunorubicin and vinblastine in the order of cyclosporin D, dihydrocyclosporin D > cyclosporin A > FK506 > cyclosporin C, dihydrocyclosporin C. The intracellular accumulation of the anticancer agents was highly associated with the transporting function of P-glycoprotein. The inhibitory effect of cyclosporin D was concentration-dependent. The inhibitory effect of the modulators on P-glycoprotein was not correlated with the immunosuppressive activity, but was correlated with their lipophilicity. Conclusions. In the transcellular transport system, lipophilicity may be one of the determinants for the inhibitory effect of various multidrug resistance modulators on the P-glycoprotein-mediated transport.

AB - Purpose. P-glycoprotein-mediated transcellular transport of anticancer agents and the inhibitory effect of cyclosporin analogs and FK506 were investigated. Methods. The transcellular transport of daunorubicin and vinblastine by monolayers of LLC-GA5-COL150 cells which overexpressed P-glycoprotein was measured in the presence and absence of cyclosporins or FK506. Results. Cyclosporins and FK506 inhibited P-glycoprotein-mediated transport of daunorubicin and vinblastine in the order of cyclosporin D, dihydrocyclosporin D > cyclosporin A > FK506 > cyclosporin C, dihydrocyclosporin C. The intracellular accumulation of the anticancer agents was highly associated with the transporting function of P-glycoprotein. The inhibitory effect of cyclosporin D was concentration-dependent. The inhibitory effect of the modulators on P-glycoprotein was not correlated with the immunosuppressive activity, but was correlated with their lipophilicity. Conclusions. In the transcellular transport system, lipophilicity may be one of the determinants for the inhibitory effect of various multidrug resistance modulators on the P-glycoprotein-mediated transport.

KW - Cyclosporine

KW - Daunorubicin

KW - FK506

KW - P-glycoprotein

KW - Vinblastine

UR - http://www.scopus.com/inward/record.url?scp=0029739719&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029739719&partnerID=8YFLogxK

U2 - 10.1023/A:1016019010339

DO - 10.1023/A:1016019010339

M3 - Article

C2 - 8842048

AN - SCOPUS:0029739719

VL - 13

SP - 1073

EP - 1077

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 7

ER -