Partial circumvention of multi-drug resistance by Annamycin is associated with comparable inhibition of DNA synthesis in the nuclear matrix of sensitive and resistant cells

Y. H. Ling, Yiyu Zou, W. Priebe, Roman Perez-Soler

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We studied the subcellular and subnuclear distributions of the partially cross-resistant anthracycline Annamycin (Ann) in KB-3-1 and multi-drug resistant KB-V1 cells. Subcellular drug localization was assessed qualitatively, by fluorescence microscopy and quantitatively by cell fractionation and fluorescence measurements. Doxorubicin (Dox) localized predominantly in the nucleus in KB-3-1 cells and in the membranes in KB-V1 cells. In contrast, the subcellular distribution of Ann was identical in both cell lines, with preferential drug localization in the perinuclear region, Golgi apparatus, endoplasmic reticulum and endosomes. Dox rate of efflux from the nucleus was negligible in KB-3-1 cells but markedly enhanced in KB-V1 cells, whereas Ann was lost at a similar rate from the nucleus in both cell lines. In KB-3-1 cells Dox levels in the nuclear non-matrix were about 2-fold higher than those of Ann, while in the matrix the inverse relationship was observed. In spite of these differences, Dox and Ann had a similar inhibitory effect on new DNA synthesis in the nuclear matrix and non-matrix of KB-3-1 cells. Dox levels were reduced by 10-fold in the nuclear non-matrix and 2-fold in the matrix in KB-V1 cells compared with KB-3-1 cells, whereas Ann levels were reduced by about 2- to 3-fold in the non-matrix and were unchanged in the matrix. In correlation with these findings, Dox did not cause inhibition of new DNA synthesis in either nuclear fraction in KB-V1 cells, whereas inhibition of new DNA synthesis in the matrix by Ann was similar in both cell lines. Our results indicate that Ann's partial circumvention of multi-drug resistance is associated with its ability to cause comparable new DNA synthesis inhibition in the nuclear matrix of sensitive and resistant cells. o 1995 Wilty-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)402-408
Number of pages7
JournalInternational Journal of Cancer
Volume61
Issue number3
StatePublished - 1995
Externally publishedYes

Fingerprint

Nuclear Matrix
Multiple Drug Resistance
KB Cells
Doxorubicin
DNA
Cell Line
Pharmaceutical Preparations
Cell Fractionation
Endosomes
Anthracyclines
Golgi Apparatus
annamycin
Fluorescence Microscopy
Endoplasmic Reticulum
Fluorescence
Cell Membrane

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{03d5d2759f1043f4ade570fcfa36e2c8,
title = "Partial circumvention of multi-drug resistance by Annamycin is associated with comparable inhibition of DNA synthesis in the nuclear matrix of sensitive and resistant cells",
abstract = "We studied the subcellular and subnuclear distributions of the partially cross-resistant anthracycline Annamycin (Ann) in KB-3-1 and multi-drug resistant KB-V1 cells. Subcellular drug localization was assessed qualitatively, by fluorescence microscopy and quantitatively by cell fractionation and fluorescence measurements. Doxorubicin (Dox) localized predominantly in the nucleus in KB-3-1 cells and in the membranes in KB-V1 cells. In contrast, the subcellular distribution of Ann was identical in both cell lines, with preferential drug localization in the perinuclear region, Golgi apparatus, endoplasmic reticulum and endosomes. Dox rate of efflux from the nucleus was negligible in KB-3-1 cells but markedly enhanced in KB-V1 cells, whereas Ann was lost at a similar rate from the nucleus in both cell lines. In KB-3-1 cells Dox levels in the nuclear non-matrix were about 2-fold higher than those of Ann, while in the matrix the inverse relationship was observed. In spite of these differences, Dox and Ann had a similar inhibitory effect on new DNA synthesis in the nuclear matrix and non-matrix of KB-3-1 cells. Dox levels were reduced by 10-fold in the nuclear non-matrix and 2-fold in the matrix in KB-V1 cells compared with KB-3-1 cells, whereas Ann levels were reduced by about 2- to 3-fold in the non-matrix and were unchanged in the matrix. In correlation with these findings, Dox did not cause inhibition of new DNA synthesis in either nuclear fraction in KB-V1 cells, whereas inhibition of new DNA synthesis in the matrix by Ann was similar in both cell lines. Our results indicate that Ann's partial circumvention of multi-drug resistance is associated with its ability to cause comparable new DNA synthesis inhibition in the nuclear matrix of sensitive and resistant cells. o 1995 Wilty-Liss, Inc.",
author = "Ling, {Y. H.} and Yiyu Zou and W. Priebe and Roman Perez-Soler",
year = "1995",
language = "English (US)",
volume = "61",
pages = "402--408",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Partial circumvention of multi-drug resistance by Annamycin is associated with comparable inhibition of DNA synthesis in the nuclear matrix of sensitive and resistant cells

AU - Ling, Y. H.

AU - Zou, Yiyu

AU - Priebe, W.

AU - Perez-Soler, Roman

PY - 1995

Y1 - 1995

N2 - We studied the subcellular and subnuclear distributions of the partially cross-resistant anthracycline Annamycin (Ann) in KB-3-1 and multi-drug resistant KB-V1 cells. Subcellular drug localization was assessed qualitatively, by fluorescence microscopy and quantitatively by cell fractionation and fluorescence measurements. Doxorubicin (Dox) localized predominantly in the nucleus in KB-3-1 cells and in the membranes in KB-V1 cells. In contrast, the subcellular distribution of Ann was identical in both cell lines, with preferential drug localization in the perinuclear region, Golgi apparatus, endoplasmic reticulum and endosomes. Dox rate of efflux from the nucleus was negligible in KB-3-1 cells but markedly enhanced in KB-V1 cells, whereas Ann was lost at a similar rate from the nucleus in both cell lines. In KB-3-1 cells Dox levels in the nuclear non-matrix were about 2-fold higher than those of Ann, while in the matrix the inverse relationship was observed. In spite of these differences, Dox and Ann had a similar inhibitory effect on new DNA synthesis in the nuclear matrix and non-matrix of KB-3-1 cells. Dox levels were reduced by 10-fold in the nuclear non-matrix and 2-fold in the matrix in KB-V1 cells compared with KB-3-1 cells, whereas Ann levels were reduced by about 2- to 3-fold in the non-matrix and were unchanged in the matrix. In correlation with these findings, Dox did not cause inhibition of new DNA synthesis in either nuclear fraction in KB-V1 cells, whereas inhibition of new DNA synthesis in the matrix by Ann was similar in both cell lines. Our results indicate that Ann's partial circumvention of multi-drug resistance is associated with its ability to cause comparable new DNA synthesis inhibition in the nuclear matrix of sensitive and resistant cells. o 1995 Wilty-Liss, Inc.

AB - We studied the subcellular and subnuclear distributions of the partially cross-resistant anthracycline Annamycin (Ann) in KB-3-1 and multi-drug resistant KB-V1 cells. Subcellular drug localization was assessed qualitatively, by fluorescence microscopy and quantitatively by cell fractionation and fluorescence measurements. Doxorubicin (Dox) localized predominantly in the nucleus in KB-3-1 cells and in the membranes in KB-V1 cells. In contrast, the subcellular distribution of Ann was identical in both cell lines, with preferential drug localization in the perinuclear region, Golgi apparatus, endoplasmic reticulum and endosomes. Dox rate of efflux from the nucleus was negligible in KB-3-1 cells but markedly enhanced in KB-V1 cells, whereas Ann was lost at a similar rate from the nucleus in both cell lines. In KB-3-1 cells Dox levels in the nuclear non-matrix were about 2-fold higher than those of Ann, while in the matrix the inverse relationship was observed. In spite of these differences, Dox and Ann had a similar inhibitory effect on new DNA synthesis in the nuclear matrix and non-matrix of KB-3-1 cells. Dox levels were reduced by 10-fold in the nuclear non-matrix and 2-fold in the matrix in KB-V1 cells compared with KB-3-1 cells, whereas Ann levels were reduced by about 2- to 3-fold in the non-matrix and were unchanged in the matrix. In correlation with these findings, Dox did not cause inhibition of new DNA synthesis in either nuclear fraction in KB-V1 cells, whereas inhibition of new DNA synthesis in the matrix by Ann was similar in both cell lines. Our results indicate that Ann's partial circumvention of multi-drug resistance is associated with its ability to cause comparable new DNA synthesis inhibition in the nuclear matrix of sensitive and resistant cells. o 1995 Wilty-Liss, Inc.

UR - http://www.scopus.com/inward/record.url?scp=0028916559&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028916559&partnerID=8YFLogxK

M3 - Article

C2 - 7729954

AN - SCOPUS:0028916559

VL - 61

SP - 402

EP - 408

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 3

ER -