Informace o publikaci

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

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NAVRÁTILOVÁ Jarmila HANKEOVÁ Tereza BENEŠ Petr ŠMARDA Jan

Rok publikování 2013
Druh Článek v odborném periodiku
Časopis / Zdroj Nutrition and Cancer
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Doi http://dx.doi.org/10.1080/01635581.2013.789118
Obor Genetika a molekulární biologie
Klíčová slova tetrathiomolybdate; neuroblastoma; glucose starvation; apoptosis; cancer therapy
Popis 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.
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