Interaction between the anticancer drug cisplatin and the copper chaperone Atox1 in human melanoma cells

Palm-Espling, MariaUmeå universitet,Kemiska institutionen,Pernilla Wittung-Stafshede (författare)

Cisplatin (CisPt) is one of the most common anticancer drugs used against many severe forms of cancers. However, treatment with this drug causes many side effects and often, it results in the development of cell resistance. A majority of side effects as well as cell resistance are thought to develop due to CisPt interactions with proteins prior to reaching the nucleus and the DNA target. The copper (Cu) transport proteins Ctr1 and ATP7A/B have been implicated in cellular resistance of CisPt, possibly exporting the drug out of the cell. Recent in vitro work demonstrated that CisPt also interacts with the cytoplasmic Cu-chaperone Atox1, binding in or near the Cu-binding site, without expulsion of bound Cu. Whereas Ctr1 and ATP7B interactions with CisPt have been shown in vivo or ex vivo, there is no such information for Atox1-CisPt interactions. To address this, we developed a method to probe if CisPt interacts with Atox1 in human melanoma cells. Atox1-specific antibodies were linked to magnetic beads and used to immune-precipitate Atox1 from melanoma cells that had been pre-exposed to CisPt. Analysis of extracted Atox1 with inductively coupled plasma mass spectrometry demonstrated the presence of Pt in the protein fraction. Thus, CisPt-exposed human melanoma cells contain Atox1 molecules that bind some derivative of CisPt. This study gives the first indication for the intracellular presence of Atox1-CisPt complexes ex vivo. © 2014 Bentham Science Publishers.

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kirurgi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Surgery hsv//eng
NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
Anticancer
Atox1
Cisplatin
Copper chaperone
Immunoprecipitation
Resistance
antineoplastic agent
Atox1 protein
cell protein
chaperone
copper
unclassified drug
article
binding site
cell lysate
cytoplasm
ex vivo study
gene targeting
human
human cell
in vitro study
in vivo study
mass spectrometry
melanoma
protein interaction
protein transport
Copper-chaperone
biologisk kemi

Lundin, ChristinaUmeå universitet,Kirurgi,Peter Naredi(Swepub:umu)chlu0008 (författare)
Björn, ErikUmeå universitet,Kemiska institutionen(Swepub:umu)erkbjn97 (författare)
Naredi, Peter,1955Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery,Kirurgi, Sahlgrenska sjukhuset, Göteborgs universitet(Swepub:umu)pena0001 (författare)
Wittung-Stafshede, PernillaUmeå universitet,Kemiska institutionen(Swepub:umu)pewi0014 (författare)
Umeå universitetKemiska institutionen (creator_code:org_t)

Ingår i:Protein Peptide Letters: Bentham Science Publishers Ltd.21:1, s. 63-680929-86651875-5305

Av författaren/redakt...: Palm-Espling, Ma ...; Lundin, Christin ...; Björn, Erik; Naredi, Peter, 1 ...; Wittung-Stafshed ...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Kirurgi

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.