Chemical-proteomics Identify Peroxiredoxin-1 as an Actionable Target in Triple-negative Breast Cancer Article Swipe
Elena Spínola-Lasso
,
Juan Carlos Montero
,
Roberto Jiménez‐Monzón
,
Francisco Estévez
,
José M. Quintana
,
Borja Guerra
,
Khaled M. Elokely
,
Francisco León
,
Henoc del Rosario
,
Leandro Fernández‐Pérez
,
Manuel Rodríguez López
,
B.N. Díaz-Chico
,
Grant McNaughton‐Smith
,
Atanasio Pandiella
,
JC Diaz-Chico
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.7150/ijbs.78554
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.7150/ijbs.78554
Triple-negative breast cancer (TNBC) is difficult to treat; therefore, the development of drugs directed against its oncogenic vulnerabilities is a desirable goal. Herein, we report the antitumor effects of CM728, a novel quinone-fused oxazepine, against this malignancy. CM728 potently inhibited TNBC cell viability and decreased the growth of MDA-MB-231-induced orthotopic tumors. Furthermore, CM728 exerted a strong synergistic antiproliferative effect with docetaxel in vitro and this combination was more effective than the individual treatments in vivo. Chemical proteomic approaches revealed that CM728 bound to peroxiredoxin-1 (Prdx1), thereby inducing its oxidation. Molecular docking corroborated these findings. CM728 induced oxidative stress and a multi-signal response, including JNK/p38 MAPK activation and STAT3 inhibition. Interestingly, Prdx1 downregulation mimicked these effects. Finally, CM728 led to DNA damage, cell cycle blockage at the S and G2/M phases, and the activation of caspase-dependent apoptosis. Taken together, our results identify a novel compound with antitumoral properties against TNBC. In addition, we describe the mechanism of action of this drug and provide a rationale for the use of Prdx1 inhibitors, such as CM728, alone or in combination with other drugs, for the treatment of TNBC.
Related Topics
Concepts
Triple-negative breast cancer
Cancer research
Downregulation and upregulation
Apoptosis
Chemistry
MAPK/ERK pathway
DNA damage
p38 mitogen-activated protein kinases
In vivo
Pharmacology
Cancer
Breast cancer
Signal transduction
Biology
Biochemistry
DNA
Gene
Biotechnology
Genetics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.7150/ijbs.78554
- https://www.ijbs.com/v19p1731.pdf
- OA Status
- gold
- Cited By
- 12
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4364321312
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4364321312Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.7150/ijbs.78554Digital Object Identifier
- Title
-
Chemical-proteomics Identify Peroxiredoxin-1 as an Actionable Target in Triple-negative Breast CancerWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-01-01Full publication date if available
- Authors
-
Elena Spínola-Lasso, Juan Carlos Montero, Roberto Jiménez‐Monzón, Francisco Estévez, José M. Quintana, Borja Guerra, Khaled M. Elokely, Francisco León, Henoc del Rosario, Leandro Fernández‐Pérez, Manuel Rodríguez López, B.N. Díaz-Chico, Grant McNaughton‐Smith, Atanasio Pandiella, JC Diaz-ChicoList of authors in order
- Landing page
-
https://doi.org/10.7150/ijbs.78554Publisher landing page
- PDF URL
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https://www.ijbs.com/v19p1731.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.ijbs.com/v19p1731.pdfDirect OA link when available
- Concepts
-
Triple-negative breast cancer, Cancer research, Downregulation and upregulation, Apoptosis, Chemistry, MAPK/ERK pathway, DNA damage, p38 mitogen-activated protein kinases, In vivo, Pharmacology, Cancer, Breast cancer, Signal transduction, Biology, Biochemistry, DNA, Gene, Biotechnology, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
12Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 9, 2024: 1, 2023: 2Per-year citation counts (last 5 years)
- References (count)
-
53Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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