Sakine Akar1, Hamiyet Donmez-Altuntas2,3, Zuhal Hamurcu2,3. 1. Department of Medical Biology, Faculty of Medicine, Yuzuncu Yıl University, 65090, Van, Turkey. ylmzsakine@gmail.com. 2. Department of Medical Biology, Faculty of Medicine, Erciyes University, 38030, Kayseri, Turkey. 3. Betul-Ziya Eren Genome and Stem Cell Center (GENKOK), 38030, Kayseri, Turkey.
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.
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.
Authors: Soeun Park; Jung Min Park; Minsu Park; Dongmi Ko; Seongjae Kim; Juyeon Seo; Kee Dal Nam; Eunsun Jung; Lee Farrand; Yoon-Jae Kim; Ji Young Kim; Jae Hong Seo Journal: Cancer Cell Int Date: 2022-09-20 Impact factor: 6.429