Low-Glucose Conditions of Tumor Microenvironment enhance
cytotoxicity of tetrathiomolybdate to neuroblastoma cells

J 2013

Low-Glucose Conditions of Tumor Microenvironment enhance cytotoxicity of tetrathiomolybdate to neuroblastoma cells

NAVRÁTILOVÁ, Jarmila, Tereza HANKEOVÁ, Petr BENEŠ and Jan ŠMARDA

Basic information

Original name

Low-Glucose Conditions of Tumor Microenvironment enhance cytotoxicity of tetrathiomolybdate to neuroblastoma cells

Authors

NAVRÁTILOVÁ, Jarmila (203 Czech Republic, belonging to the institution), Tereza HANKEOVÁ (203 Czech Republic, belonging to the institution), Petr BENEŠ (203 Czech Republic, belonging to the institution) and Jan ŠMARDA (203 Czech Republic, guarantor, belonging to the institution)

Edition

Nutrition and Cancer, 2013, 0163-5581

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 2.635

RIV identification code

RIV/00216224:14310/13:00065615

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1080/01635581.2013.789118

UT WoS

000321887700010

Keywords in English

tetrathiomolybdate; neuroblastoma; glucose starvation; apoptosis; cancer therapy

Abstract

V originále

Growth of tumor cells depends on sufficient supply of fermentable substrate, such as glucose. This provokes development of new anti-cancer therapies based on dietary restrictions. However, some tumor cells can lower their glucose dependency and activate processes of ATP formation/saving to retain viability even in limited glucose supply. In addition, tumor cells often loose sensitivity to many conventional anti-cancer drugs in the low-glucose conditions. Thus, development of the drugs effectively killing the tumor cells in nutrient-limited conditions is necessary. In this study, we show an enhanced cytotoxicity of tetrathiomolybdate, the drug exhibiting anti-angiogenic and tumor-suppressing effects, to neuroblastoma SH-SY5Y and SK-N-BE(2) cells in the low-glucose conditions. This preference results from the tetrathiomolybdate-induced upregulation of cell dependency on glucose. The cells treated with tetrathiomolybdate increase the uptake of glucose, production of lactate, activate the Akt- and AMPK signaling pathways and down-regulate COX IV. In cells growing in the low-glucose conditions, these events result in significant decrease of the intracellular ATP supply and apoptosis. We propose TM as suitable agent to be used in combination with dietary restrictions in therapy of neuroblastoma.

Links

CZ.1.07/2.3.00/20.0097, interní kód MU

Name: IntegRECAMO: Intellectual Anchor (Acronym: IntegRECAMO)

Investor: Ministry of Education, Youth and Sports of the CR, 2.3 Human resources in research and development

GA301/09/1115, research and development project

Name: Úloha proteinů c-Myb a Cox-2 při tvorbě střevních nádorů

Investor: Czech Science Foundation, The role of c-Myb and Cox-2 proteins in colon carcinogenesis

NT13441, research and development project

Name: Exprese proteinů rodiny Myb v adenokarcinomech tlustého střeva a vztah k jejich metastatickému potenciálu

Citovat

NAVRÁTILOVÁ, Jarmila, Tereza HANKEOVÁ, Petr BENEŠ and Jan ŠMARDA. Low-Glucose Conditions of Tumor Microenvironment enhance cytotoxicity of tetrathiomolybdate to neuroblastoma cells. Nutrition and Cancer. 2013, vol. 65, No 5, p. 702-710. ISSN 0163-5581. Available from: https://dx.doi.org/10.1080/01635581.2013.789118.

@article{1116067,
   author = {Navrátilová, Jarmila and Hankeová, Tereza and Beneš, Petr and Šmarda, Jan},
   article_number = {5},
   doi = {http://dx.doi.org/10.1080/01635581.2013.789118},
   keywords = {tetrathiomolybdate; neuroblastoma; glucose starvation; apoptosis; cancer therapy},
   language = {eng},
   issn = {0163-5581},
   journal = {Nutrition and Cancer},
   title = {Low-Glucose Conditions of Tumor Microenvironment enhance cytotoxicity of tetrathiomolybdate to neuroblastoma cells},
   volume = {65},
   year = {2013}
}

TY  - JOUR
ID  - 1116067
AU  - Navrátilová, Jarmila - Hankeová, Tereza - Beneš, Petr - Šmarda, Jan
PY  - 2013
TI  - Low-Glucose Conditions of Tumor Microenvironment enhance cytotoxicity of tetrathiomolybdate to neuroblastoma cells
JF  - Nutrition and Cancer
VL  - 65
IS  - 5
SP  - 702-710
EP  - 702-710
SN  - 01635581
KW  - tetrathiomolybdate
KW  - neuroblastoma
KW  - glucose starvation
KW  - apoptosis
KW  - cancer therapy
N2  - Growth of tumor cells depends on sufficient supply of fermentable substrate, such as glucose. This provokes development of new anti-cancer therapies based on dietary restrictions. However, some tumor cells can lower their glucose dependency and activate processes of ATP formation/saving to retain viability even in limited glucose supply. In addition, tumor cells often loose sensitivity to many conventional anti-cancer drugs in the low-glucose conditions. Thus, development of the drugs effectively killing the tumor cells in nutrient-limited conditions is necessary. In this study, we show an enhanced cytotoxicity of tetrathiomolybdate, the drug exhibiting anti-angiogenic and tumor-suppressing effects, to neuroblastoma SH-SY5Y and SK-N-BE(2) cells in the low-glucose conditions. This preference results from the tetrathiomolybdate-induced upregulation of cell dependency on glucose. The cells treated with tetrathiomolybdate increase the uptake of glucose, production of lactate, activate the Akt- and AMPK signaling pathways and down-regulate COX IV. In cells growing in the low-glucose conditions, these events result in significant decrease of the intracellular ATP supply and apoptosis. We propose TM as suitable agent to be used in combination with dietary restrictions in therapy of neuroblastoma.
ER  -

NAVRÁTILOVÁ, Jarmila, Tereza HANKEOVÁ, Petr BENEŠ and Jan ŠMARDA. Low-Glucose Conditions of Tumor Microenvironment enhance cytotoxicity of tetrathiomolybdate to neuroblastoma cells. \textit{Nutrition and Cancer}. 2013, vol.~65, No~5, p.~702-710. ISSN~0163-5581. Available from: https://dx.doi.org/10.1080/01635581.2013.789118.

Detailed Information on Publication Record