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Caffeic acid phenet...
Caffeic acid phenethyl ester targets ubiquitin-specific protease 8 and synergizes with cisplatin in endometrioid ovarian carcinoma cells
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- Colombo, Diego (author)
- Univ Milan, Italy
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- Gatti, Laura (author)
- Fdn IRCCS Ist Neurol Carlo Besta, Italy
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- Sjöstrand, Linda (author)
- Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten
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- Carenini, Nives (author)
- Fdn IRCCS Ist Nazl Tumori, Italy
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- Costantino, Matteo (author)
- Fdn IRCCS Ist Nazl Tumori, Italy
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- Corna, Elisabetta (author)
- Fdn IRCCS Ist Nazl Tumori, Italy
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- Arrighetti, Noemi (author)
- Fdn IRCCS Ist Nazl Tumori, Italy
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- Zuccolo, Marco (author)
- Univ Milan, Italy
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- De Cesare, Michelandrea (author)
- Fdn IRCCS Ist Nazl Tumori, Italy
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- Linder, Stig (author)
- Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Karolinska Inst, Sweden
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- D´arcy, Padraig (author)
- Karolinska Institutet,Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten
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- Perego, Paola (author)
- Fdn IRCCS Ist Nazl Tumori, Italy
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(creator_code:org_t)
- PERGAMON-ELSEVIER SCIENCE LTD, 2022
- 2022
- English.
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In: Biochemical Pharmacology. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0006-2952 .- 1356-1839 .- 1873-2968. ; 197
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Subject headings
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- Deubiquitinases (DUBs) mediate the removal of ubiquitin from diverse proteins that participate in the regulation of cell survival, DNA damage repair, apoptosis and drug resistance. Previous studies have shown an association between activation of cell survival pathways and platinum-drug resistance in ovarian carcinoma cell lines. Among the strategies available to inhibit DUBs, curcumin derivatives appear promising, thus we hypothesized their use to enhance the efficacy of cisplatin in ovarian carcinoma preclinical models. The caffeic acid phenethyl ester (CAPE), inhibited ubiquitin-specific protease 8 (USP8), but not proteasomal DUBs in cell-free assays. When CAPE was combined with cisplatin in nine cell lines representative of various histotypes a synergistic effect was observed in TOV112D cells and in the cisplatin-resistant IGROV-1/Pt1 variant, both of endometrioid type and carrying mutant TP53. In the latter cells, persistent G1 accumulation upon combined treatment associated with p27(kip1) protein levels was observed. The synergy was not dependent on apoptosis induction, and appeared to occur in cells with higher USP8 levels. In vivo antitumor activity studies supported the advantage of the combination of CAPE and cisplatin in the subcutaneous model of cisplatin-resistant IGROV-1/Pt1 ovarian carcinoma as well as CAPE activity on intraperitoneal disease. This study reveals the therapeutic potential of CAPE in cisplatin-resistant ovarian tumors as well as in tumors expressing USP8.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Cisplatin resistance; Ovarian carcinoma; Deubiquitinases; USP8
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Colombo, Diego
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Gatti, Laura
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Sjöstrand, Linda
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Carenini, Nives
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Costantino, Matt ...
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Corna, Elisabett ...
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show more...
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Arrighetti, Noem ...
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Zuccolo, Marco
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De Cesare, Miche ...
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Linder, Stig
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D´arcy, Padraig
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Perego, Paola
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Biochemical Phar ...
- By the university
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Linköping University
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Karolinska Institutet