Pharmacogenomics of cantharidin in tumor cells

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

Pharmacogenomics of cantharidin in tumor cells

Standard

Pharmacogenomics of cantharidin in tumor cells. / Kadioglu, Onat; Salehi-Kermani, Navid; Kelter, Gerhard; Schumacher, Udo; Fiebig, Heinz-Herbert; Greten, Henry Johannes; Efferth, Thomas.

In: BIOCHEM PHARMACOL, Vol. 87, No. 3, 01.02.2014, p. 399-409.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kadioglu, O, Salehi-Kermani, N, Kelter, G, Schumacher, U, Fiebig, H-H, Greten, HJ & Efferth, T 2014, 'Pharmacogenomics of cantharidin in tumor cells', BIOCHEM PHARMACOL, vol. 87, no. 3, pp. 399-409. https://doi.org/10.1016/j.bcp.2013.10.025

APA

Kadioglu, O., Salehi-Kermani, N., Kelter, G., Schumacher, U., Fiebig, H-H., Greten, H. J., & Efferth, T. (2014). Pharmacogenomics of cantharidin in tumor cells. BIOCHEM PHARMACOL, 87(3), 399-409. https://doi.org/10.1016/j.bcp.2013.10.025

Vancouver

Kadioglu O, Salehi-Kermani N, Kelter G, Schumacher U, Fiebig H-H, Greten HJ et al. Pharmacogenomics of cantharidin in tumor cells. BIOCHEM PHARMACOL. 2014 Feb 1;87(3):399-409. https://doi.org/10.1016/j.bcp.2013.10.025

Bibtex

@article{407f03874b584f249b738a7ab1870eae,

title = "Pharmacogenomics of cantharidin in tumor cells",

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.",

keywords = "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",

author = "Onat Kadioglu and Navid Salehi-Kermani and Gerhard Kelter and Udo Schumacher and Heinz-Herbert Fiebig and Greten, {Henry Johannes} and Thomas Efferth",

year = "2014",

month = feb,

day = "1",

doi = "10.1016/j.bcp.2013.10.025",

language = "English",

volume = "87",

pages = "399--409",

journal = "BIOCHEM PHARMACOL",

issn = "0006-2952",

publisher = "Elsevier Inc.",

number = "3",

}

RIS

TY - JOUR

T1 - Pharmacogenomics of cantharidin in tumor cells

AU - Kadioglu, Onat

AU - Salehi-Kermani, Navid

AU - Kelter, Gerhard

AU - Schumacher, Udo

AU - Fiebig, Heinz-Herbert

AU - Greten, Henry Johannes

AU - Efferth, Thomas

PY - 2014/2/1

Y1 - 2014/2/1

N2 - 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.

AB - 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.

KW - Animals

KW - Binding Sites

KW - Cantharidin

KW - Cell Line, Tumor

KW - Gene Expression Regulation, Enzymologic

KW - Humans

KW - Models, Molecular

KW - Molecular Structure

KW - Oligonucleotide Array Sequence Analysis

KW - Pharmacogenetics

KW - Protein Conformation

KW - RNA, Messenger

KW - Receptors, Neuropeptide Y

U2 - 10.1016/j.bcp.2013.10.025

DO - 10.1016/j.bcp.2013.10.025

M3 - SCORING: Journal article

C2 - 24231507

VL - 87

SP - 399

EP - 409

JO - BIOCHEM PHARMACOL

JF - BIOCHEM PHARMACOL

SN - 0006-2952

IS - 3

ER -