Substituted Steroidal Compounds Containing Amino and Amido Groups Reverse Multidrug Resistance of Mouse T-Lymphoma and Two Human Prostate Cancer Cell Lines In Vitro

Publication type:
Journal article
Metadata:
Autoren
  • Akos Csonka
  • Sami Hamdoun
  • Gabriella Spengler
  • Ana Martins
  • Iren Vincze
  • Thomas Efferth
  • Joseph Molnar
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000352731600031&DestLinkType=FullRecord&DestApp=WOS_CPL
eISSN
1791-7530
Externe Identifier
  • Clarivate Analytics Document Solution ID: CF7JF
  • PubMed Identifier: 25862866
ISSN
0250-7005
Ausgabe der Veröffentlichung
4
Zeitschrift
ANTICANCER RESEARCH
Schlüsselwörter
  • steroids
  • multidrug resistance
  • ABCB1 transporter
  • mouse T-lymphoma
  • PC-3 prostate cancer cell line
Paginierung
2105 - 2112
Datum der Veröffentlichung
2015
Status
Published
Titel
Substituted Steroidal Compounds Containing Amino and Amido Groups Reverse Multidrug Resistance of Mouse T-Lymphoma and Two Human Prostate Cancer Cell Lines <i>In Vitro</i>
Sub types
  • Article
Ausgabe der Zeitschrift
35

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<h4>Background</h4>Resistance to chemotherapy is a main problem in cancer. The search for new effective compounds that can increase sensitivity of resistant cells to existing chemotherapeutics is an urgent need. In previous studies, it has been demonstrated that steroid derivatives showed promising results concerning their capacity to modulate resistance of multidrug-resistant cell lines.<h4>Materials and methods</h4>Steroid derivatives were studied for their growth-inhibitory effect, cytotoxicity, reversal of multidrug resistance, apoptosis induction, and interaction with doxorubicin on multidrug resistant human ATP-binding cassette, sub-family B, member 1 (ABCB1) gene-transfected mouse T-lymphoma cell line, and human PC-3 and LNCaP prostate cancer cell lines in vitro. The steroidal interaction with P-glycoprotein (ABCB1) was investigated by molecular docking.<h4>Results</h4>Both the activity of steroid derivatives on inhibition of the ABCB1 pump and their interaction with doxorubicin are dependent on the substituent groups of the investigated steroidal structures. Even though the investigated steroid derivatives were found to have limited antiproliferative effect on the three different cancer cell lines, in combination with doxorubicin, most of them acted as good potentiators. The binding energies from molecular docking ranged from -6.43 to -9.88 kcal/mol. The predicted inhibition constants ranged from 0.1 to 10.1 μM. A significant negative correlation was found between binding energy and fluorescence activity ratio (R=-0.5, p=0.015).<h4>Conclusion</h4>The effective compounds can be candidates of model molecules for possible application in the treatment of multidrug resistant cancer in rational drug design.
Addresses
  • Institute of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary Department of Traumatology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Autoren
  • Ákos Csonka
  • Sami Hamdoun
  • Gabriella Spengler
  • Ana Martins
  • Irén Vincze
  • Thomas Efferth
  • Joseph Molnár
eISSN
1791-7530
Externe Identifier
  • PubMed Identifier: 25862866
Open access
false
ISSN
0250-7005
Ausgabe der Veröffentlichung
4
Zeitschrift
Anticancer research
Schlüsselwörter
  • Cell Line, Tumor
  • Animals
  • Humans
  • Mice
  • Lymphoma, T-Cell
  • Prostatic Neoplasms
  • Doxorubicin
  • Drug Resistance, Multiple
  • Apoptosis
  • Drug Resistance, Neoplasm
  • Male
  • In Vitro Techniques
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
Sprache
eng
Medium
Print
Paginierung
2105 - 2112
Datum der Veröffentlichung
2015
Status
Published
Datum der Datenerfassung
2015
Titel
Substituted steroidal compounds containing amino and amido groups reverse multidrug resistance of mouse T-lymphoma and two human prostate cancer cell lines in vitro.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
35

Data source: Europe PubMed Central

Abstract
BACKGROUND: Resistance to chemotherapy is a main problem in cancer. The search for new effective compounds that can increase sensitivity of resistant cells to existing chemotherapeutics is an urgent need. In previous studies, it has been demonstrated that steroid derivatives showed promising results concerning their capacity to modulate resistance of multidrug-resistant cell lines. MATERIALS AND METHODS: Steroid derivatives were studied for their growth-inhibitory effect, cytotoxicity, reversal of multidrug resistance, apoptosis induction, and interaction with doxorubicin on multidrug resistant human ATP-binding cassette, sub-family B, member 1 (ABCB1) gene-transfected mouse T-lymphoma cell line, and human PC-3 and LNCaP prostate cancer cell lines in vitro. The steroidal interaction with P-glycoprotein (ABCB1) was investigated by molecular docking. RESULTS: Both the activity of steroid derivatives on inhibition of the ABCB1 pump and their interaction with doxorubicin are dependent on the substituent groups of the investigated steroidal structures. Even though the investigated steroid derivatives were found to have limited antiproliferative effect on the three different cancer cell lines, in combination with doxorubicin, most of them acted as good potentiators. The binding energies from molecular docking ranged from -6.43 to -9.88 kcal/mol. The predicted inhibition constants ranged from 0.1 to 10.1 μM. A significant negative correlation was found between binding energy and fluorescence activity ratio (R=-0.5, p=0.015). CONCLUSION: The effective compounds can be candidates of model molecules for possible application in the treatment of multidrug resistant cancer in rational drug design.
Autoren
  • Ákos Csonka
  • Sami Hamdoun
  • Gabriella Spengler
  • Ana Martins
  • Irén Vincze
  • Thomas Efferth
  • Joseph Molnár
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/25862866
eISSN
1791-7530
Ausgabe der Veröffentlichung
4
Zeitschrift
Anticancer Res
Schlüsselwörter
  • ABCB1 transporter
  • PC-3 prostate cancer cell line
  • mouse T-lymphoma
  • multidrug resistance
  • steroids
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Doxorubicin
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Humans
  • In Vitro Techniques
  • Lymphoma, T-Cell
  • Male
  • Mice
  • Prostatic Neoplasms
Sprache
eng
Country
Greece
Paginierung
2105 - 2112
PII
35/4/2105
Datum der Veröffentlichung
2015
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2015
Titel
Substituted steroidal compounds containing amino and amido groups reverse multidrug resistance of mouse T-lymphoma and two human prostate cancer cell lines in vitro.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
35

Data source: PubMed

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