Universität zu Köln

Kullmann, Maximilian, Kalayda, Ganna V., Hellwig, Malte ORCID: 0000-0002-9239-956X, Kotz, Sandra, Hilger, Ralf A., Metzger, Sabine and Jaehde, Ulrich (2015). Assessing the contribution of the two protein disulfide isomerases PDIA1 and PDIA3 to cisplatin resistance. J. Inorg. Biochem., 153. S. 247 - 253. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1873-3344

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Abstract

Intracellular binding of cisplatin to non-DNA partners, such as proteins, has received increasing attention as an additional mode of action and as mechanism of resistance. We investigated two cisplatin-interacting isoforms of protein disulfide isomerase regarding their contribution to acquired cisplatin resistance using sensitive and resistant A2780/A2780cis ovarian cancer cells. Cisplatin cytotoxicity was assessed after knockdown of either protein disulfide isomerase family A member 1 (PDIA1) or protein disulfide isomerase family A member 3 (PDIA3). Whereas PDIA1 knockdown led to increased cytotoxicity in resistant A2780cis cells, PDIA3 knockdown showed no influence on cytotoxicity. Coincubation with propynoic acid carbamoyl methyl amide 31 (PACMA31), a PDIA1 inhibitor, resensitized A2780cis cells to cisplatin treatment Determination of the combination index revealed that the combination of cisplafin and PACMA31 acts synergistically. Our results warrant further evaluation of PDIA1 as promising target for chemotherapy, and its inhibition by PACMA31 as a new therapeutic approach. (C) 2015 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kullmann, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalayda, Ganna V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hellwig, Malte UNSPECIFIED orcid.org/0000-0002-9239-956X UNSPECIFIED Kotz, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Hilger, Ralf A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzger, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaehde, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-384849
DOI:	10.1016/j.jinorgbio.2015.08.028
Journal or Publication Title:	J. Inorg. Biochem.
Volume:	153
Page Range:	S. 247 - 253
Date:	2015
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1873-3344
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INDUCED CELL-DEATH; DRUG-COMBINATION; CANCER; APOPTOSIS; METALLOTHIONEIN; SENSITIVITY; KNOCKDOWN; ADDUCTS; ANALOG; ER-60 Multiple languages Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38484