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β-Escin reduces cancer progression in aggressive MDA-MB-231 cells by inhibiting glutamine metabolism through downregulation of c-myc oncogene

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Abstract

Background

The c-myc oncogene, which causes glutamine dependence in triple negative breast cancers (TNBC), is also the target of one of the signaling pathways affected by β-Escin.

Methods and results

We sought to determine how c-myc protein affects glutamine metabolism and the proteins, glutamine transporter alanine-serine-cysteine 2 (ASCT2) and glutaminase (GLS1), in β-Escin-treated MDA-MB-231 cells using glutamine uptake and western blot analysis. Cell viability, colony formation, migration and apoptosis were also evaluated in MDA-MB-231 cells in response to β-Escin treatment using MTS, colony forming, wound healing, and Annexin-V assay. We determined that β-Escin decreased glutamine uptake and reduced c-myc and GLS1 protein expressions and increased the expression of ASCT2. In addition, this inhibition of glutamine metabolism decreased cell proliferation, colony formation and migration, and induced apoptosis.

Conclusions

In this study, it was suggested that β-Escin inhibits glutamine metabolism via c-myc in MDA-MB-231 cells, and it is thought that as a result of interrupting the energy supply in these cells via c-myc, it results in a decrease in the carcinogenic properties of the cells. Consequently, β-Escin may be promising as a therapeutic agent for glutamine-dependent cancers.

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Acknowledgements

This work was financially supported by the Scientific and Technological Research Council of Turkey (TUBITAK). Research Grant (Grant number: 119S227).

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Authors and Affiliations

  1. Department of Medical Biology, Faculty of Medicine, Yuzuncu Yıl University, 65090, Van, Turkey

    Sakine AKAR

  2. Department of Medical Biology, Faculty of Medicine, Erciyes University, 38030, Kayseri, Turkey

    Hamiyet DONMEZ-ALTUNTAS & Zuhal HAMURCU

  3. Betul-Ziya Eren Genome and Stem Cell Center (GENKOK), 38030, Kayseri, Turkey

    Hamiyet DONMEZ-ALTUNTAS & Zuhal HAMURCU

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  1. Sakine AKAR
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  2. Hamiyet DONMEZ-ALTUNTAS
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  3. Zuhal HAMURCU
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Correspondence to Sakine AKAR.

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AKAR, S., DONMEZ-ALTUNTAS, H. & HAMURCU, Z. β-Escin reduces cancer progression in aggressive MDA-MB-231 cells by inhibiting glutamine metabolism through downregulation of c-myc oncogene. Mol Biol Rep 49, 7409–7415 (2022). https://doi.org/10.1007/s11033-022-07536-5

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  • DOI: https://doi.org/10.1007/s11033-022-07536-5

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