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

Akar S., ALTUNTAŞ H., HAMURCU Z.

Molecular Biology Reports, vol.49, no.8, pp.7409-7415, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 49 Issue: 8
  • Publication Date: 2022
  • Doi Number: 10.1007/s11033-022-07536-5
  • Journal Name: Molecular Biology Reports
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.7409-7415
  • Keywords: Apoptosis, ASCT2, Breast cancer, beta-Escin, Glutamine, GLS1, Migration, c-myc, MDA-MB-231, BREAST-CANCER, SUPPRESSES PROLIFERATION, IN-VITRO, KAPPA-B, APOPTOSIS, RESISTANCE, MIGRATION, INVASION, GEMCITABINE, EXPRESSION
  • Kayseri University Affiliated: No

Abstract

© 2022, The Author(s), under exclusive licence to Springer Nature B.V.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.