In Silico Analysis of Microarray-Based Gene Expression Profiles Predicts Tumor Cell Response to Withanolides

Publication type:
Journal article
Metadata:
Autoren
DOI
10.3390/microarrays1010044
eISSN
2076-3905
Ausgabe der Veröffentlichung
1
Zeitschrift
Microarrays
Sprache
en
Online publication date
2012
Paginierung
44 - 63
Status
Published online
Herausgeber
MDPI AG
Herausgeber URL
http://dx.doi.org/10.3390/microarrays1010044
Datum der Datenerfassung
2022
Titel
In Silico Analysis of Microarray-Based Gene Expression Profiles Predicts Tumor Cell Response to Withanolides
Ausgabe der Zeitschrift
1

Data source: Crossref

Other metadata sources:
Abstract
Withania somnifera (L.) Dunal (Indian ginseng, winter cherry, Solanaceae) is widely used in traditional medicine. Roots are either chewed or used to prepare beverages (aqueous decocts). The major secondary metabolites of Withania somnifera are the withanolides, which are C-28-steroidal lactone triterpenoids. Withania somnifera extracts exert chemopreventive and anticancer activities in vitro and in vivo. The aims of the present in silico study were, firstly, to investigate whether tumor cells develop cross-resistance between standard anticancer drugs and withanolides and, secondly, to elucidate the molecular determinants of sensitivity and resistance of tumor cells towards withanolides. Using IC50 concentrations of eight different withanolides (withaferin A, withaferin A diacetate, 3-azerininylwithaferin A, withafastuosin D diacetate, 4-B-hydroxy-withanolide E, isowithanololide E, withafastuosin E, and withaperuvin) and 19 established anticancer drugs, we analyzed the cross-resistance profile of 60 tumor cell lines. The cell lines revealed cross-resistance between the eight withanolides. Consistent cross-resistance between withanolides and nitrosoureas (carmustin, lomustin, and semimustin) was also observed. Then, we performed transcriptomic microarray-based COMPARE and hierarchical cluster analyses of mRNA expression to identify mRNA expression profiles predicting sensitivity or resistance towards withanolides. Genes from diverse functional groups were significantly associated with response of tumor cells to withaferin A diacetate, e.g. genes functioning in DNA damage and repair, stress response, cell growth regulation, extracellular matrix components, cell adhesion and cell migration, constituents of the ribosome, cytoskeletal organization and regulation, signal transduction, transcription factors, and others.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, Mainz 55128, Germany. efferth@uni-mainz.de.
Autoren
DOI
10.3390/microarrays1010044
eISSN
2076-3905
Externe Identifier
  • PubMed Identifier: 27605335
  • PubMed Central ID: PMC5007710
Open access
true
ISSN
2076-3905
Ausgabe der Veröffentlichung
1
Zeitschrift
Microarrays (Basel, Switzerland)
Sprache
eng
Medium
Electronic
Online publication date
2012
Open access status
Open Access
Paginierung
44 - 63
Datum der Veröffentlichung
2012
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2016
Titel
In Silico Analysis of Microarray-Based Gene Expression Profiles Predicts Tumor Cell Response to Withanolides.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
1

Files

https://www.mdpi.com/2076-3905/1/1/44/pdf?version=1337693663 https://europepmc.org/articles/PMC5007710?pdf=render

Data source: Europe PubMed Central

Abstract
Withania somnifera (L.) Dunal (Indian ginseng, winter cherry, Solanaceae) is widely used in traditional medicine. Roots are either chewed or used to prepare beverages (aqueous decocts). The major secondary metabolites of Withania somnifera are the withanolides, which are C-28-steroidal lactone triterpenoids. Withania somnifera extracts exert chemopreventive and anticancer activities in vitro and in vivo. The aims of the present in silico study were, firstly, to investigate whether tumor cells develop cross-resistance between standard anticancer drugs and withanolides and, secondly, to elucidate the molecular determinants of sensitivity and resistance of tumor cells towards withanolides. Using IC50 concentrations of eight different withanolides (withaferin A, withaferin A diacetate, 3-azerininylwithaferin A, withafastuosin D diacetate, 4-B-hydroxy-withanolide E, isowithanololide E, withafastuosin E, and withaperuvin) and 19 established anticancer drugs, we analyzed the cross-resistance profile of 60 tumor cell lines. The cell lines revealed cross-resistance between the eight withanolides. Consistent cross-resistance between withanolides and nitrosoureas (carmustin, lomustin, and semimustin) was also observed. Then, we performed transcriptomic microarray-based COMPARE and hierarchical cluster analyses of mRNA expression to identify mRNA expression profiles predicting sensitivity or resistance towards withanolides. Genes from diverse functional groups were significantly associated with response of tumor cells to withaferin A diacetate, e.g. genes functioning in DNA damage and repair, stress response, cell growth regulation, extracellular matrix components, cell adhesion and cell migration, constituents of the ribosome, cytoskeletal organization and regulation, signal transduction, transcription factors, and others.
Date of acceptance
2012
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/27605335
DOI
10.3390/microarrays1010044
Externe Identifier
  • PubMed Central ID: PMC5007710
ISSN
2076-3905
Ausgabe der Veröffentlichung
1
Zeitschrift
Microarrays (Basel)
Schlüsselwörter
  • cancer
  • drug development
  • medicinal food
  • microarray
  • natural products
  • pharmacogenomics
Sprache
eng
Country
Switzerland
Paginierung
44 - 63
PII
microarrays1010044
Datum der Veröffentlichung
2012
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2016
Titel
In Silico Analysis of Microarray-Based Gene Expression Profiles Predicts Tumor Cell Response to Withanolides.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
1

Data source: PubMed

Beziehungen:
Property of

Tools