Kinome-Wide Profiling Identifies Human WNK3 as a Target of Cajanin Stilbene Acid from Cajanus cajan (L.) Millsp.

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000756060800001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.3390/ijms23031506
eISSN
1422-0067
Externe Identifier
  • Clarivate Analytics Document Solution ID: ZA3IE
  • PubMed Identifier: 35163434
Ausgabe der Veröffentlichung
3
Zeitschrift
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Schlüsselwörter
  • cancer
  • food crop
  • mode-of-action
  • natural products
  • nutrition
  • targeted therapy
Artikelnummer
ARTN 1506
Datum der Veröffentlichung
2022
Status
Published
Titel
Kinome-Wide Profiling Identifies Human WNK3 as a Target of Cajanin Stilbene Acid from <i>Cajanus cajan</i> (L.) Millsp.
Sub types
  • Article
Ausgabe der Zeitschrift
23

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:p>Pigeon Pea (Cajanus cajan (L.) Millsp.) is a common food crop used in many parts of the world for nutritional purposes. One of its chemical constituents is cajanin stilbene acid (CSA), which exerts anticancer activity in vitro and in vivo. In an effort to identify molecular targets of CSA, we performed a kinome-wide approach based on the measurement of the enzymatic activities of 252 human kinases. The serine-threonine kinase WNK3 (also known as protein kinase lysine-deficient 3) was identified as the most promising target of CSA with the strongest enzymatic activity inhibition in vitro and the highest binding affinity in molecular docking in silico. The lowest binding affinity and the predicted binding constant pKi of CSA (−9.65 kcal/mol and 0.084 µM) were comparable or even better than those of the known WNK3 inhibitor PP-121 (−9.42 kcal/mol and 0.123 µM). The statistically significant association between WNK3 mRNA expression and cellular responsiveness to several clinically established anticancer drugs in a panel of 60 tumor cell lines and the prognostic value of WNK3 mRNA expression in sarcoma biopsies for the survival time of 230 patients can be taken as clues that CSA-based inhibition of WNK3 may improve treatment outcomes of cancer patients and that CSA may serve as a valuable supplement to the currently used combination therapy protocols in oncology.</jats:p>
Autoren
DOI
10.3390/ijms23031506
eISSN
1422-0067
Ausgabe der Veröffentlichung
3
Zeitschrift
International Journal of Molecular Sciences
Sprache
en
Online publication date
2022
Paginierung
1506 - 1506
Status
Published online
Herausgeber
MDPI AG
Herausgeber URL
http://dx.doi.org/10.3390/ijms23031506
Datum der Datenerfassung
2022
Titel
Kinome-Wide Profiling Identifies Human WNK3 as a Target of Cajanin Stilbene Acid from Cajanus cajan (L.) Millsp.
Ausgabe der Zeitschrift
23

Data source: Crossref

Abstract
Pigeon Pea (<i>Cajanus cajan</i> (L.) Millsp.) is a common food crop used in many parts of the world for nutritional purposes. One of its chemical constituents is cajanin stilbene acid (CSA), which exerts anticancer activity in vitro and in vivo. In an effort to identify molecular targets of CSA, we performed a kinome-wide approach based on the measurement of the enzymatic activities of 252 human kinases. The serine-threonine kinase WNK3 (also known as protein kinase lysine-deficient 3) was identified as the most promising target of CSA with the strongest enzymatic activity inhibition in vitro and the highest binding affinity in molecular docking in silico. The lowest binding affinity and the predicted binding constant pKi of CSA (-9.65 kcal/mol and 0.084 µM) were comparable or even better than those of the known WNK3 inhibitor PP-121 (-9.42 kcal/mol and 0.123 µM). The statistically significant association between WNK3 mRNA expression and cellular responsiveness to several clinically established anticancer drugs in a panel of 60 tumor cell lines and the prognostic value of WNK3 mRNA expression in sarcoma biopsies for the survival time of 230 patients can be taken as clues that CSA-based inhibition of WNK3 may improve treatment outcomes of cancer patients and that CSA may serve as a valuable supplement to the currently used combination therapy protocols in oncology.
Addresses
  • Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey.
Autoren
DOI
10.3390/ijms23031506
eISSN
1422-0067
Externe Identifier
  • PubMed Identifier: 35163434
  • PubMed Central ID: PMC8835736
Open access
true
ISSN
1422-0067
Ausgabe der Veröffentlichung
3
Zeitschrift
International journal of molecular sciences
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • Cajanus
  • Neoplasms
  • Salicylates
  • Stilbenes
  • Protein Kinases
  • Survival Analysis
  • Down-Regulation
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Binding Sites
  • Protein Conformation
  • Protein Binding
  • Models, Molecular
  • Kaplan-Meier Estimate
  • Molecular Docking Simulation
  • Protein Serine-Threonine Kinases
Sprache
eng
Medium
Electronic
Online publication date
2022
Open access status
Open Access
Paginierung
1506
Datum der Veröffentlichung
2022
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2022
Titel
Kinome-Wide Profiling Identifies Human WNK3 as a Target of Cajanin Stilbene Acid from <i>Cajanus cajan</i> (L.) Millsp.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
23

Files

https://www.mdpi.com/1422-0067/23/3/1506/pdf?version=1643377104 https://europepmc.org/articles/PMC8835736?pdf=render

Data source: Europe PubMed Central

Abstract
Pigeon Pea (Cajanus cajan (L.) Millsp.) is a common food crop used in many parts of the world for nutritional purposes. One of its chemical constituents is cajanin stilbene acid (CSA), which exerts anticancer activity in vitro and in vivo. In an effort to identify molecular targets of CSA, we performed a kinome-wide approach based on the measurement of the enzymatic activities of 252 human kinases. The serine-threonine kinase WNK3 (also known as protein kinase lysine-deficient 3) was identified as the most promising target of CSA with the strongest enzymatic activity inhibition in vitro and the highest binding affinity in molecular docking in silico. The lowest binding affinity and the predicted binding constant pKi of CSA (-9.65 kcal/mol and 0.084 µM) were comparable or even better than those of the known WNK3 inhibitor PP-121 (-9.42 kcal/mol and 0.123 µM). The statistically significant association between WNK3 mRNA expression and cellular responsiveness to several clinically established anticancer drugs in a panel of 60 tumor cell lines and the prognostic value of WNK3 mRNA expression in sarcoma biopsies for the survival time of 230 patients can be taken as clues that CSA-based inhibition of WNK3 may improve treatment outcomes of cancer patients and that CSA may serve as a valuable supplement to the currently used combination therapy protocols in oncology.
Date of acceptance
2022
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/35163434
DOI
10.3390/ijms23031506
eISSN
1422-0067
Externe Identifier
  • PubMed Central ID: PMC8835736
Ausgabe der Veröffentlichung
3
Zeitschrift
Int J Mol Sci
Schlüsselwörter
  • cancer
  • food crop
  • mode-of-action
  • natural products
  • nutrition
  • targeted therapy
  • Binding Sites
  • Cajanus
  • Cell Line, Tumor
  • Down-Regulation
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Models, Molecular
  • Molecular Docking Simulation
  • Neoplasms
  • Protein Binding
  • Protein Conformation
  • Protein Kinases
  • Protein Serine-Threonine Kinases
  • Salicylates
  • Stilbenes
  • Survival Analysis
Sprache
eng
Country
Switzerland
PII
ijms23031506
Datum der Veröffentlichung
2022
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Titel
Kinome-Wide Profiling Identifies Human WNK3 as a Target of Cajanin Stilbene Acid from Cajanus cajan (L.) Millsp.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
23

Data source: PubMed

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