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, cilt.49, sa.8, ss.7409-7415, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 49 Sayı: 8
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1007/s11033-022-07536-5
  • Dergi Adı: Molecular Biology Reports
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.7409-7415
  • Anahtar Kelimeler: 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
  • Erciyes Üniversitesi Adresli: Evet

Özet

© 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.