Pharmacogenomics of cantharidin in tumor cells

Autoren

Onat Kadioglu
Navid Salehi Kermani
Gerhard Kelter
Udo Schumacher
Heinz-Herbert Fiebig
Henry Johannes Greten
Thomas Efferth

DOI

10.1016/j.bcp.2013.10.025

ISSN

0006-2952

Ausgabe der Veröffentlichung

3

Zeitschrift

Biochemical Pharmacology

Sprache

en

Paginierung

399 - 409

Datum der Veröffentlichung

2014

Status

Published

Herausgeber

Elsevier BV

Herausgeber URL

http://dx.doi.org/10.1016/j.bcp.2013.10.025

Datum der Datenerfassung

2019

Titel

Pharmacogenomics of cantharidin in tumor cells

Ausgabe der Zeitschrift

87

Data source: Crossref

Abstract

Cantharis vesicatoria (blister beetle) is used in Chinese medicine and has been categorized as highly toxic in the Chinese pharmacopeia. In Europe, Cantharis patches have been used since ages to treat various skin-related diseases. We investigated the cytotoxicity of the Cantharis ingredient, cantharidin, in 41 tumor cell lines (Oncotest panel) and compared the results with those of 60 cell lines of the National Cancer Institute, USA. We found profound activity at low micromolar concentrations (log ₁₀IC₅₀ values between -6.980 and 5.009 M). Cantharidin bound to protein phosphatase 2A (PP2A) with higher affinity (-8.12 kcal/mol) than to PP1 (-6.25 kcal/mol) in molecular docking analyses. Using a PCR array for 84 apoptosis genes, cantharidin treatment upregulated gene expression of caspase-1 and nerve growth factor receptor, but downregulated mRNA expression of Bcl-2 like protein 10, Fas ligand, and tumor necrosis factor-α. By using COMPARE analysis of microarray-based transcriptome-wide mRNA expressions, 21 genes were found to significantly correlate with response of 60 tumor cell lines to cantharidin. As shown by hierarchical cluster analysis and chi-squared test, the distribution of cell lines in the dendrogram according to their gene expression profiles predicted sensitivity or resistance to cantharidin (P=6.482 × 10(-5)). The compassionate use of Cantharis patches in two patients suffering from basalioma and Mycosis fungoides, respectively, considerably improved the diseases without signs of toxicity. In conclusion, these results indicate that cantharidin may be a useful candidate to develop novel strategies for cancer therapy.

Addresses

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.

Autoren

Onat Kadioglu
Navid Salehi Kermani
Gerhard Kelter
Udo Schumacher
Heinz-Herbert Fiebig
Henry Johannes Greten
Thomas Efferth
Thomas Efferth

DOI

10.1016/j.bcp.2013.10.025

eISSN

1873-2968

Externe Identifier

PubMed Identifier: 24231507

Open access

false

ISSN

0006-2952

Ausgabe der Veröffentlichung

3

Zeitschrift

Biochemical pharmacology

Schlüsselwörter

Cell Line, Tumor
Animals
Humans
Cantharidin
Receptors, Neuropeptide Y
RNA, Messenger
Oligonucleotide Array Sequence Analysis
Pharmacogenetics
Gene Expression Regulation, Enzymologic
Binding Sites
Molecular Structure
Protein Conformation
Models, Molecular

Sprache

eng

Medium

Print-Electronic

Online publication date

2013

Paginierung

399 - 409

Datum der Veröffentlichung

2014

Status

Published

Datum der Datenerfassung

2013

Titel

Pharmacogenomics of cantharidin in tumor cells.

Sub types

Journal Article

Ausgabe der Zeitschrift

87

Data source: Europe PubMed Central

Abstract

Cantharis vesicatoria (blister beetle) is used in Chinese medicine and has been categorized as highly toxic in the Chinese pharmacopeia. In Europe, Cantharis patches have been used since ages to treat various skin-related diseases. We investigated the cytotoxicity of the Cantharis ingredient, cantharidin, in 41 tumor cell lines (Oncotest panel) and compared the results with those of 60 cell lines of the National Cancer Institute, USA. We found profound activity at low micromolar concentrations (log ₁₀IC₅₀ values between -6.980 and 5.009 M). Cantharidin bound to protein phosphatase 2A (PP2A) with higher affinity (-8.12 kcal/mol) than to PP1 (-6.25 kcal/mol) in molecular docking analyses. Using a PCR array for 84 apoptosis genes, cantharidin treatment upregulated gene expression of caspase-1 and nerve growth factor receptor, but downregulated mRNA expression of Bcl-2 like protein 10, Fas ligand, and tumor necrosis factor-α. By using COMPARE analysis of microarray-based transcriptome-wide mRNA expressions, 21 genes were found to significantly correlate with response of 60 tumor cell lines to cantharidin. As shown by hierarchical cluster analysis and chi-squared test, the distribution of cell lines in the dendrogram according to their gene expression profiles predicted sensitivity or resistance to cantharidin (P=6.482 × 10(-5)). The compassionate use of Cantharis patches in two patients suffering from basalioma and Mycosis fungoides, respectively, considerably improved the diseases without signs of toxicity. In conclusion, these results indicate that cantharidin may be a useful candidate to develop novel strategies for cancer therapy.

Date of acceptance

2013

Autoren

Onat Kadioglu
Navid Salehi Kermani
Gerhard Kelter
Udo Schumacher
Heinz-Herbert Fiebig
Henry Johannes Greten
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/24231507

DOI

10.1016/j.bcp.2013.10.025

eISSN

1873-2968

Ausgabe der Veröffentlichung

3

Zeitschrift

Biochem Pharmacol

Schlüsselwörter

Blister beetle
Cancer
Cantharidin
Microarray
Protein phosphatase
Animals
Binding Sites
Cantharidin
Cell Line, Tumor
Gene Expression Regulation, Enzymologic
Humans
Models, Molecular
Molecular Structure
Oligonucleotide Array Sequence Analysis
Pharmacogenetics
Protein Conformation
RNA, Messenger
Receptors, Neuropeptide Y

Sprache

eng

Country

England

Paginierung

399 - 409

PII

S0006-2952(13)00709-0

Datum der Veröffentlichung

2014

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2014

Titel

Pharmacogenomics of cantharidin in tumor cells.

Sub types

Journal Article

Ausgabe der Zeitschrift

87

Data source: PubMed

Pharmacogenomics of cantharidin in tumor cells

Tools