Ultrastructural effects of colchicine, vinblastine, and taxol in drug-sensitive and multidrug-resistant J 774.2 cells

E. B. Masurovsky, Susan Band Horwitz

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cell lines derived from the murine macrophage-like cell J 774.2 are resistant to the cytotoxic effects of colchicine, vinblastine, and taxol. These multidrug-resistant (MDR) cells overproduce a family of ∼ 130-150 kDa P-glycoproteins (P-gp) associated with the plasma membrane region and display other typical features of the MDR phenotype. Ultrastructural analysis of drug-treated cells indicated that although hallmark structural effects engendered by each drug at efficacious doses were profound in the drug-sensitive J 774.2 cells, they were not evident in the similarly treated MDR cell lines. Thus, MDR phenotypic expression involved maintaining drug levels at subthreshold values so as to preclude the advent of these morphologic changes, and allowed vital tubulin-associated cellular processes, including replication, to occur. Using a polyclonal antibody specific for the P-gp, electron microscopic immunocytochemical evidence is presented for substantial association of P-gp with the plasma membrane/cell surface in the resistant cells which was not demonstrable in the drug-sensitive J 774.2 cells. This key cell surface localization of P-gp is germane to the postulated transport and related mechanisms whereby P-gp may play a pivotal role in endowing cells with multidrug resistance.

Original languageEnglish (US)
Pages (from-to)138-149
Number of pages12
JournalProtoplasma
Volume148
Issue number2-3
DOIs
StatePublished - Jun 1989

Fingerprint

vinblastine
paclitaxel
Vinblastine
colchicine
Colchicine
Paclitaxel
P-Glycoproteins
drugs
Pharmaceutical Preparations
cells
Cell Membrane
plasma membrane
cell lines
Cell Line
Multiple Drug Resistance
Tubulin
Plasma Cells
multiple drug resistance
tubulin
polyclonal antibodies

Keywords

  • Colchicine
  • J 774.2-cells
  • Multidrug resistance
  • Taxol
  • Vinblastine

ASJC Scopus subject areas

  • Cell Biology
  • Plant Science

Cite this

Ultrastructural effects of colchicine, vinblastine, and taxol in drug-sensitive and multidrug-resistant J 774.2 cells. / Masurovsky, E. B.; Band Horwitz, Susan.

In: Protoplasma, Vol. 148, No. 2-3, 06.1989, p. 138-149.

Research output: Contribution to journalArticle

@article{59d4f1ea309d49f094abfb38f7b2022d,
title = "Ultrastructural effects of colchicine, vinblastine, and taxol in drug-sensitive and multidrug-resistant J 774.2 cells",
abstract = "Cell lines derived from the murine macrophage-like cell J 774.2 are resistant to the cytotoxic effects of colchicine, vinblastine, and taxol. These multidrug-resistant (MDR) cells overproduce a family of ∼ 130-150 kDa P-glycoproteins (P-gp) associated with the plasma membrane region and display other typical features of the MDR phenotype. Ultrastructural analysis of drug-treated cells indicated that although hallmark structural effects engendered by each drug at efficacious doses were profound in the drug-sensitive J 774.2 cells, they were not evident in the similarly treated MDR cell lines. Thus, MDR phenotypic expression involved maintaining drug levels at subthreshold values so as to preclude the advent of these morphologic changes, and allowed vital tubulin-associated cellular processes, including replication, to occur. Using a polyclonal antibody specific for the P-gp, electron microscopic immunocytochemical evidence is presented for substantial association of P-gp with the plasma membrane/cell surface in the resistant cells which was not demonstrable in the drug-sensitive J 774.2 cells. This key cell surface localization of P-gp is germane to the postulated transport and related mechanisms whereby P-gp may play a pivotal role in endowing cells with multidrug resistance.",
keywords = "Colchicine, J 774.2-cells, Multidrug resistance, Taxol, Vinblastine",
author = "Masurovsky, {E. B.} and {Band Horwitz}, Susan",
year = "1989",
month = "6",
doi = "10.1007/BF02079333",
language = "English (US)",
volume = "148",
pages = "138--149",
journal = "Protoplasma",
issn = "0033-183X",
publisher = "Springer Wien",
number = "2-3",

}

TY - JOUR

T1 - Ultrastructural effects of colchicine, vinblastine, and taxol in drug-sensitive and multidrug-resistant J 774.2 cells

AU - Masurovsky, E. B.

AU - Band Horwitz, Susan

PY - 1989/6

Y1 - 1989/6

N2 - Cell lines derived from the murine macrophage-like cell J 774.2 are resistant to the cytotoxic effects of colchicine, vinblastine, and taxol. These multidrug-resistant (MDR) cells overproduce a family of ∼ 130-150 kDa P-glycoproteins (P-gp) associated with the plasma membrane region and display other typical features of the MDR phenotype. Ultrastructural analysis of drug-treated cells indicated that although hallmark structural effects engendered by each drug at efficacious doses were profound in the drug-sensitive J 774.2 cells, they were not evident in the similarly treated MDR cell lines. Thus, MDR phenotypic expression involved maintaining drug levels at subthreshold values so as to preclude the advent of these morphologic changes, and allowed vital tubulin-associated cellular processes, including replication, to occur. Using a polyclonal antibody specific for the P-gp, electron microscopic immunocytochemical evidence is presented for substantial association of P-gp with the plasma membrane/cell surface in the resistant cells which was not demonstrable in the drug-sensitive J 774.2 cells. This key cell surface localization of P-gp is germane to the postulated transport and related mechanisms whereby P-gp may play a pivotal role in endowing cells with multidrug resistance.

AB - Cell lines derived from the murine macrophage-like cell J 774.2 are resistant to the cytotoxic effects of colchicine, vinblastine, and taxol. These multidrug-resistant (MDR) cells overproduce a family of ∼ 130-150 kDa P-glycoproteins (P-gp) associated with the plasma membrane region and display other typical features of the MDR phenotype. Ultrastructural analysis of drug-treated cells indicated that although hallmark structural effects engendered by each drug at efficacious doses were profound in the drug-sensitive J 774.2 cells, they were not evident in the similarly treated MDR cell lines. Thus, MDR phenotypic expression involved maintaining drug levels at subthreshold values so as to preclude the advent of these morphologic changes, and allowed vital tubulin-associated cellular processes, including replication, to occur. Using a polyclonal antibody specific for the P-gp, electron microscopic immunocytochemical evidence is presented for substantial association of P-gp with the plasma membrane/cell surface in the resistant cells which was not demonstrable in the drug-sensitive J 774.2 cells. This key cell surface localization of P-gp is germane to the postulated transport and related mechanisms whereby P-gp may play a pivotal role in endowing cells with multidrug resistance.

KW - Colchicine

KW - J 774.2-cells

KW - Multidrug resistance

KW - Taxol

KW - Vinblastine

UR - http://www.scopus.com/inward/record.url?scp=0038140903&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038140903&partnerID=8YFLogxK

U2 - 10.1007/BF02079333

DO - 10.1007/BF02079333

M3 - Article

VL - 148

SP - 138

EP - 149

JO - Protoplasma

JF - Protoplasma

SN - 0033-183X

IS - 2-3

ER -