Assessing the contribution of the two protein disulfide isomerases PDIA1 and PDIA3 to cisplatin resistance

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Assessing the contribution of the two protein disulfide isomerases PDIA1 and PDIA3 to cisplatin resistance. / Kullmann, Maximilian; Kalayda, Ganna V; Hellwig, Malte; Kotz, Sandra; Hilger, Ralf A; Metzger, Sabine; Jaehde, Ulrich.

In: J INORG BIOCHEM, Vol. 153, 12.2015, p. 247-252.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Kullmann, M, Kalayda, GV, Hellwig, M, Kotz, S, Hilger, RA, Metzger, S & Jaehde, U 2015, 'Assessing the contribution of the two protein disulfide isomerases PDIA1 and PDIA3 to cisplatin resistance', J INORG BIOCHEM, vol. 153, pp. 247-252. https://doi.org/10.1016/j.jinorgbio.2015.08.028

APA

Kullmann, M., Kalayda, G. V., Hellwig, M., Kotz, S., Hilger, R. A., Metzger, S., & Jaehde, U. (2015). Assessing the contribution of the two protein disulfide isomerases PDIA1 and PDIA3 to cisplatin resistance. J INORG BIOCHEM, 153, 247-252. https://doi.org/10.1016/j.jinorgbio.2015.08.028

Vancouver

Bibtex

@article{f2d06db4dfb9406f83e21a57cbdbe936,
title = "Assessing the contribution of the two protein disulfide isomerases PDIA1 and PDIA3 to cisplatin resistance",
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 cisplatin 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. ",
keywords = "Antineoplastic Agents/chemistry, Cell Line, Tumor, Cisplatin/chemistry, Drug Resistance, Neoplasm, Enzyme Inhibitors/pharmacology, Humans, Procollagen-Proline Dioxygenase/antagonists & inhibitors, Protein Binding, Protein Disulfide-Isomerases/antagonists & inhibitors",
author = "Maximilian Kullmann and Kalayda, {Ganna V} and Malte Hellwig and Sandra Kotz and Hilger, {Ralf A} and Sabine Metzger and Ulrich Jaehde",
note = "Copyright {\textcopyright} 2015 Elsevier Inc. All rights reserved.",
year = "2015",
month = dec,
doi = "10.1016/j.jinorgbio.2015.08.028",
language = "English",
volume = "153",
pages = "247--252",
journal = "J INORG BIOCHEM",
issn = "0162-0134",
publisher = "Elsevier Inc.",

}

RIS

TY - JOUR

T1 - Assessing the contribution of the two protein disulfide isomerases PDIA1 and PDIA3 to cisplatin resistance

AU - Kullmann, Maximilian

AU - Kalayda, Ganna V

AU - Hellwig, Malte

AU - Kotz, Sandra

AU - Hilger, Ralf A

AU - Metzger, Sabine

AU - Jaehde, Ulrich

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/12

Y1 - 2015/12

N2 - 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 cisplatin 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.

AB - 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 cisplatin 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.

KW - Antineoplastic Agents/chemistry

KW - Cell Line, Tumor

KW - Cisplatin/chemistry

KW - Drug Resistance, Neoplasm

KW - Enzyme Inhibitors/pharmacology

KW - Humans

KW - Procollagen-Proline Dioxygenase/antagonists & inhibitors

KW - Protein Binding

KW - Protein Disulfide-Isomerases/antagonists & inhibitors

U2 - 10.1016/j.jinorgbio.2015.08.028

DO - 10.1016/j.jinorgbio.2015.08.028

M3 - SCORING: Journal article

C2 - 26364260

VL - 153

SP - 247

EP - 252

JO - J INORG BIOCHEM

JF - J INORG BIOCHEM

SN - 0162-0134

ER -