Monensin Inhibits Canonical Wnt Signaling in Human Colorectal
Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal
Neoplasia Mice

J 2014

Monensin Inhibits Canonical Wnt Signaling in Human Colorectal Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal Neoplasia Mice

TŮMOVÁ, Lucie, Antonio POMBINHO, Martina VOJTĚCHOVÁ, Jitka STANČÍKOVÁ, Dietmar GRADL et. al.

Basic information

Original name

Monensin Inhibits Canonical Wnt Signaling in Human Colorectal Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal Neoplasia Mice

Authors

TŮMOVÁ, Lucie (203 Czech Republic), Antonio POMBINHO (620 Portugal), Martina VOJTĚCHOVÁ (203 Czech Republic), Jitka STANČÍKOVÁ (203 Czech Republic), Dietmar GRADL (276 Germany), Michaela KRAUSOVÁ (203 Czech Republic), Eva ŠLONCOVÁ (203 Czech Republic), Monika HORÁZNÁ (203 Czech Republic), Vítězslav KŘÍŽ (203 Czech Republic), Olga MACHOŇOVÁ (203 Czech Republic), Jindřich JINDŘICH (203 Czech Republic), Zbyněk ZDRÁHAL (203 Czech Republic, guarantor, belonging to the institution), Petr BARTŮNĚK (203 Czech Republic) and Vladimír KOŘÍNEK (203 Czech Republic)

Edition

Molecular Cancer Therapeutics, Philadelphia, American Association for Cancer Research, 2014, 1535-7163

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.683

RIV identification code

RIV/00216224:14740/14:00075743

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1158/1535-7163.MCT-13-0625

UT WoS

000334342300005

Keywords in English

BETA-CATENIN; CYCLE ARREST; COLON-CANCER; CARCINOMA-CELLS; LEUKEMIA-CELLS; IN-VIVO; APOPTOSIS; ACTIVATION; APC; GENES

Abstract

V originále

The Wnt signaling pathway is required during embryonic development and for the maintenance of homeostasis in adult tissues. However, aberrant activation of the pathway is implicated in a number of human disorders, including cancer of the gastrointestinal tract, breast, liver, melanoma, and hematologic malignancies. In this study, we identified monensin, a polyether ionophore antibiotic, as a potent inhibitor of Wnt signaling. The inhibitory effect of monensin on the Wnt/beta-catenin signaling cascade was observed in mammalian cells stimulated with Wnt ligands, glycogen synthase kinase-3 inhibitors, and in cells transfected with beta-catenin expression constructs. Furthermore, monensin suppressed the Wnt-dependent tail fin regeneration in zebrafish and Wnt- or beta-catenin-induced formation of secondary body axis in Xenopus embryos. In Wnt3a-activated HEK293 cells, monensin blocked the phoshorylation of Wnt coreceptor low-density lipoprotein receptor related protein 6 and promoted its degradation. In human colorectal carcinoma cells displaying deregulated Wnt signaling, monensin reduced the intracellular levels of beta-catenin. The reduction attenuated the expression of Wnt signaling target genes such as cyclin D1 and SP5 and decreased the cell proliferation rate. In multiple intestinal neoplasia (Min) mice, daily administration of monensin suppressed progression of the intestinal tumors without any sign of toxicity on normal mucosa. Our data suggest monensin as a prospective anticancer drug for therapy of neoplasia with deregulated Wnt signaling.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

Citovat

TŮMOVÁ, Lucie, Antonio POMBINHO, Martina VOJTĚCHOVÁ, Jitka STANČÍKOVÁ, Dietmar GRADL, Michaela KRAUSOVÁ, Eva ŠLONCOVÁ, Monika HORÁZNÁ, Vítězslav KŘÍŽ, Olga MACHOŇOVÁ, Jindřich JINDŘICH, Zbyněk ZDRÁHAL, Petr BARTŮNĚK and Vladimír KOŘÍNEK. Monensin Inhibits Canonical Wnt Signaling in Human Colorectal Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal Neoplasia Mice. Molecular Cancer Therapeutics. Philadelphia: American Association for Cancer Research, 2014, vol. 13, No 4, p. 812-822. ISSN 1535-7163. Available from: https://dx.doi.org/10.1158/1535-7163.MCT-13-0625.

@article{1186351,
   author = {Tůmová, Lucie and Pombinho, Antonio and Vojtěchová, Martina and Stančíková, Jitka and Gradl, Dietmar and Krausová, Michaela and Šloncová, Eva and Horázná, Monika and Kříž, Vítězslav and Machoňová, Olga and Jindřich, Jindřich and Zdráhal, Zbyněk and Bartůněk, Petr and Kořínek, Vladimír},
   article_location = {Philadelphia},
   article_number = {4},
   doi = {http://dx.doi.org/10.1158/1535-7163.MCT-13-0625},
   keywords = {BETA-CATENIN; CYCLE ARREST; COLON-CANCER; CARCINOMA-CELLS; LEUKEMIA-CELLS; IN-VIVO; APOPTOSIS; ACTIVATION; APC; GENES},
   language = {eng},
   issn = {1535-7163},
   journal = {Molecular Cancer Therapeutics},
   title = {Monensin Inhibits Canonical Wnt Signaling in Human Colorectal Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal Neoplasia Mice},
   url = {http://mct.aacrjournals.org/content/13/4/812.long},
   volume = {13},
   year = {2014}
}

TY  - JOUR
ID  - 1186351
AU  - Tůmová, Lucie - Pombinho, Antonio - Vojtěchová, Martina - Stančíková, Jitka - Gradl, Dietmar - Krausová, Michaela - Šloncová, Eva - Horázná, Monika - Kříž, Vítězslav - Machoňová, Olga - Jindřich, Jindřich - Zdráhal, Zbyněk - Bartůněk, Petr - Kořínek, Vladimír
PY  - 2014
TI  - Monensin Inhibits Canonical Wnt Signaling in Human Colorectal Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal Neoplasia Mice
JF  - Molecular Cancer Therapeutics
VL  - 13
IS  - 4
SP  - 812-822
EP  - 812-822
PB  - American Association for Cancer Research
SN  - 15357163
KW  - BETA-CATENIN
KW  - CYCLE ARREST
KW  - COLON-CANCER
KW  - CARCINOMA-CELLS
KW  - LEUKEMIA-CELLS
KW  - IN-VIVO
KW  - APOPTOSIS
KW  - ACTIVATION
KW  - APC
KW  - GENES
UR  - http://mct.aacrjournals.org/content/13/4/812.long
L2  - http://mct.aacrjournals.org/content/13/4/812.long
N2  - The Wnt signaling pathway is required during embryonic development and for the maintenance of homeostasis in adult tissues. However, aberrant activation of the pathway is implicated in a number of human disorders, including cancer of the gastrointestinal tract, breast, liver, melanoma, and hematologic malignancies. In this study, we identified monensin, a polyether ionophore antibiotic, as a potent inhibitor of Wnt signaling. The inhibitory effect of monensin on the Wnt/beta-catenin signaling cascade was observed in mammalian cells stimulated with Wnt ligands, glycogen synthase kinase-3 inhibitors, and in cells transfected with beta-catenin expression constructs. Furthermore, monensin suppressed the Wnt-dependent tail fin regeneration in zebrafish and Wnt- or beta-catenin-induced formation of secondary body axis in Xenopus embryos. In Wnt3a-activated HEK293 cells, monensin blocked the phoshorylation of Wnt coreceptor low-density lipoprotein receptor related protein 6 and promoted its degradation. In human colorectal carcinoma cells displaying deregulated Wnt signaling, monensin reduced the intracellular levels of beta-catenin. The reduction attenuated the expression of Wnt signaling target genes such as cyclin D1 and SP5 and decreased the cell proliferation rate. In multiple intestinal neoplasia (Min) mice, daily administration of monensin suppressed progression of the intestinal tumors without any sign of toxicity on normal mucosa. Our data suggest monensin as a prospective anticancer drug for therapy of neoplasia with deregulated Wnt signaling.
ER  -

TŮMOVÁ, Lucie, Antonio POMBINHO, Martina VOJTĚCHOVÁ, Jitka STANČÍKOVÁ, Dietmar GRADL, Michaela KRAUSOVÁ, Eva ŠLONCOVÁ, Monika HORÁZNÁ, Vítězslav KŘÍŽ, Olga MACHOŇOVÁ, Jindřich JINDŘICH, Zbyněk ZDRÁHAL, Petr BARTŮNĚK and Vladimír KOŘÍNEK. Monensin Inhibits Canonical Wnt Signaling in Human Colorectal Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal Neoplasia Mice. \textit{Molecular Cancer Therapeutics}. Philadelphia: American Association for Cancer Research, 2014, vol.~13, No~4, p.~812-822. ISSN~1535-7163. Available from: https://dx.doi.org/10.1158/1535-7163.MCT-13-0625.

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