Intracellular localisation studies of doxorubicin and Victoria Blue BO in EMT6-S and EMT6-R cells using confocal microscopy.

Abstract:

:The subcellular localisation of doxorubicin and Victoria Blue BO (VBBO) in a murine mammary tumour cell line EMT6-S, and the resistant sub-lineEMT6-R was studied, using confocal microscopy, in order to investigate their sites of action. In cells treated with doxorubicin (10 mu M) for 90 min, the pattern of intracellular drug distribution differed between the two cell lines. Doxorubicin was found to localise mainly in the nucleus of the sensitive cell line, whereas weak fluorescence was observed in the cytoplasm of the resistant cells, in a punctuate pattern, with no nuclear involvement. The drug also appeared to be effluxed more rapidly by the resistant cell line. The accumulation of doxorubicin at various time intervals over 1h in EMT6-S cells showed that the drug clearly interacted with both the plasma membrane and the nucleus. In contrast to doxorubicin, the intracellular distribution of VBBO in both EMT6-S and EMT6-R was similar, VBBO was clearly localised throughout the cytoplasm, in a punctuate pattern, which may be consistent with the widespread distribution of mitochondria. A more apical pattern of accumulation was noted in the EMT6-R cell line. No interaction with the plasma membrane was evident. These results indicate that the main modes of action for the two drugs differ markedly, suggesting involvement of both the membrane and the nucleus in the case of doxorubicin, but mitochondrial involvement for VBBO.

journal_name

Cytotechnology

journal_title

Cytotechnology

authors

Burrow SM,Phoenix DA,Wainwright M,Tobin MJ

doi

10.1023/A:1022435829894

subject

Has Abstract

pub_date

2002-05-01 00:00:00

pages

15-25

issue

1

eissn

0920-9069

issn

1573-0778

journal_volume

39

pub_type

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