Cellular uptake mechanisms of an antitumor ruthenium compound: the endosomal/lysosomal system as a target for anticancer metal-based drugs.
Microsc Microanal
; 19(5): 1122-30, 2013 Oct.
Article
em En
| MEDLINE
| ID: mdl-23790186
Previous studies have described promising antitumor activity of an organometallic Ru(II) complex, η5-cyclopentadienyl(2,2'-bipyridyl)(triphenylphosphane) Ruthenium(II) triflate ([η5-C5H5)Ru(2,2'-bipyridyl)(PPh3)][CF3SO3]) herein designated as TM34. Its broad spectrum of activity against a panel of human tumor cell lines and high antiproliferative efficiency prompted us to focus on its mode of action. We present herein results obtained with two human tumor cell lines A2780 and MDAMB231 on the compound distribution within the cell, the mechanism of its activity, and its cellular targets. The prospective metallodrug TM34 revealed: (a) fast antiproliferative effects even at short incubation times for both cell lines; (b) preferential localization at the cell membrane and cytosol; (c) cellular activity by a temperature-dependent process, probably macropinocytosis; (d) inhibition of a lysosomal enzyme, acid phosphatase, in a dose-dependent mode; and (e) disruption and vesiculation of the Golgi apparatus, which suggest the involvement of the endosomal/lysosomal system in its mode of action. These results are essential to elucidate the basis for the cytotoxic activity and mechanism of action of this Ru(II)(η5-cyclopentadienyl) complex.
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Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Endossomos
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Lisossomos
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Antineoplásicos
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article