Browsing by Author "Hamurcu, Zuhal"

Now showing 1 - 2 of 2

Downregulation of Glutaminase 1 (Gls1) Inhibits Proliferation, Clonogenicity, and Migration of Aggressive Mda-Mb Breast Cancer Cells by Increasing P21 and Decreasing Integrin-Β1 Expression
(Erciyes Univ Sch Medicine, 2022) Akar, Sakine; Donmez-Altuntas, Hamiyet; Hamurcu, Zuhal
Objective: Glutamine metabolism is an important pathway in cell proliferation and tumor progression. The first enzyme to be converted in the process of glutamine metabolism, glutaminase 1 (GLS1), exhibits increased expression in many types of cancer, including breast cancer. Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with high glutamine metabolic activity. The aim of this research was to examine the effects on glutamine metabolism and carcinogenic properties following small interfering RNA (siRNA)-mediated inhibition of GLS1 in glutamine-dependent TNBC.Materials and Methods: The effects on cell proliferation, migration, apoptosis, colony formation, and the cell cycle of MDA-MB-231 cells using different siRNAs targeting GLS1 were analyzed using an MTS assay, a wound-healing assay, clo-nogenic analysis, and annexin V and propidium iodide staining methods. The protein expression of GLS1, integrin beta 1 (beta 1), caspase-3, and p21 were examined using western blot analysis and flow cytometry.Results: The findings revealed that cell viability, migration, and colony formation were significantly suppressed in MDA-MB-231 cells transfected with 2 different GLS1 siRNAs. Furthermore, the results of flow cytometry and western blot analysis demonstrated that knockdown of GLS1 induced arrest in the G0/G1 phase of the cell cycle through the p21 signaling pathway, but did not induce apoptosis.Conclusion: GLS1 is needed for cell proliferation and promotes tumor progression and growth of MDA-MB 231 cells. siRNAs may provide a means to downregulate GLS1 and offer a promising target for breast cancer therapy.
Β-Escin Reduces Cancer Progression in Aggressive Mda-Mb Cells by Inhibiting Glutamine Metabolism Through Downregulation of C-Myc Oncogene
(Springer, 2022) Akar, Sakine; Donmez-Altuntas, Hamiyet; Hamurcu, Zuhal
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 beta-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 beta-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 beta-Escin treatment using MTS, colony forming, wound healing, and Annexin-V assay. We determined that beta-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 beta-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, beta-Escin may be promising as a therapeutic agent for glutamine-dependent cancers.