Confocal Microscopic Analysis of the Interaction between Cisplatin and the Copper Transporter ATP7B in Human Ovarian Carcinoma Cells

Abstract

ABSTRACT

Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells

“…Recent studies suggest that one mechanism by which CDDP is exported from the cell is via sequestration into vesicles of the secretory pathway (9). Because exosomes represent one of the outputs of this pathway, it was of interest to determine whether exosomes released by the CDDP-resistant cells contain more CDDP than those from the sensitive cells following loading of the cells with CDDP.…”

“…Studies of the cellular pharmacology of CDDP in cells overexpressing ATP7A and ATP7B indicate that CDDP is sequestered into vesicles belonging to the secretory pathway as well as lysosomes (7,8). Microscopic analyses with a fluoresceinconjugated CDDP have confirmed that CDDP accumulates in vesicles that contain ATP7A or ATP7B (9,10). Additional confocal microscopic analysis of fluorescein-conjugated CDDP in cells treated with drugs that inhibit trafficking pathways suggests that the accumulation of CDDP in the secretory compartment may require lysosomal function (10).…”

Interaction between the Anticancer Drug Cisplatin and the Copper Chaperone Atox1 in Human Melanoma Cells

“…ATP7A and ATP7B are homologous Cu-transporting ATPases positioned in the trans-Golgi network. CisPt has been shown to trigger re-localization of these multi-domain, membraneassociated proteins towards more peripheral parts of the cell where they are thought to mediate CisPt resistance by sequestering the drug into intra-cellular vesicles [6][7]. The ATP7A/B proteins have been found to be over-expressed in CisPt resistant cancer cells [2,8].…”

Administration of isothiocyanate (E-4IB) and cisplatin leads to altered signalling and lysosomal export in human ovarian carcinoma sensitive- and cisplatin-resistant cells

“…Several experimental data suggest that one of mechanisms by which CDDP is exported from the cells is via sequestration into vesicules of the secretory pathway [14,23]. In this context it was of interest to compare LTR-stained vesicules accumulated in-and released by the parental cells following the drug treatment.…”

“…Growing evidence indicates that CDDP is sequestered into intracellular vesicles, some of which belong to secretory pathways [10,14,23]. Therefore, we determined the efflux of the LTR dye following a single and/or combined effect of the drugs.…”