Akademik Veri Yönetim Sistemi
TuPA International Proteomics Congress // 4th Turkish National Proteomics Congress, Kocaeli, Türkiye, 11 - 12 Ekim 2024, ss.15
Objective: The rising incidence of breast cancer (BC) underscores
the urgent need for new therapeutic targets and agents to combat resistance and
toxic side effects associated with current treatments. Thymoquinone (TQ) has been shown to play a role in apoptosis, cell cycle
regulation, cell proliferation, epithelial-to-mesenchymal transition, invasion,
angiogenesis, and metastasis in various types of cancer. The anticancer mechanisms of TQ have been explored in
various studies, yet a comprehensive analysis in BC remains lacking. This study
aims to elucidate the proteomic changes induced by TQ treatment in MCF-7 BC cells
and uncover the underlying molecular mechanisms.
Methods: MCF-7 cells were treated with 15 µM TQ, the inhibitory concentration
(IC50) determined in our previous study, for 48 hours. Protein extracts from
treated and untreated control cells were analyzed using liquid
chromatography-tandem mass spectrometry (LC-MS/MS). Label-free quantitation
(LFQ) identified differentially regulated proteins, with validation through
Western blot analysis. Functional annotations were performed using the STRING
database. Annotations with a false discovery rate less than 0.05 were
considered significant. Subsequently,
functional annotations were visualized using the SRplot.
Results: The LFQ analysis identified 629 regulated proteins, with 104 upregulated
and 477 downregulated in TQ-treated cells, considering a two-fold change
between groups. Western blot analysis confirmed a significant decrease in ATP synthase subunit alpha of Complex V (ATP5A) expression (p<0.0001). Functional
annotations revealed significant enrichment in metabolic and biosynthetic
pathways, including carbon metabolism, ribosome, and amino acid biosynthesis.
Conclusion: Thymoquinone induces significant proteomic changes in
MCF-7 cells, predominantly affecting pathways related to cellular metabolism.
These findings suggest that TQ’s anticancer effects may be mediated through
metabolic reprogramming, providing insights into its potential as a therapeutic
agent for BC. In vivo validation and investigation of TQ’s long-term
effects are necessary to fully explore its therapeutic potential in metabolic
reprogramming and BC treatment.