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Updated: May 7, 2025
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Thymoquinone and Metabolic Reprogramming in Breast Cancer: A New Dimension From Proteomic Analysis
Tuğcan Korak1, Merve Gulsen Bal Albayrak1, Murat Kasap1
1Department of Medical Biology, Kocaeli University, Kocaeli, Turkey.
Abstract:
Thymoquinone (TQ) has shown antitumorigenic effects in breast cancer; however, its detailed impact on cell signaling mechanisms requires further investigation. This study aims to elucidate the molecular mechanisms behind TQ's antiproliferative effects in breast cancer by analyzing proteome-level changes. MCF-7 cells were treated with 15 µM TQ, the inhibitory concentration (IC50), for 48 h. Proteins from treated and untreated (control) groups were isolated and subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis. Identified proteins were functionally annotated, with hub proteins identified using Cytoscape software, and verification conducted through Western blot analysis. Label-free quantitation identified 629 master proteins, with 104 upregulated and 477 downregulated in TQ-treated samples compared to controls. Among these, 150 proteins showed dramatic regulation, including 11 upregulated and 139 downregulated proteins, with ribosomal proteins emerging as central. The heatmap demonstrated robust clustering of replicates. Functional annotations indicated that TQ significantly impacts crucial mechanisms such as carbon metabolism, amino acid biosynthesis, protein synthesis, and the citrate cycle, essential for metabolic reprogramming. This study identifies novel molecular targets associated with metabolic reprogramming, previously underexplored in TQ's effects, highlighting their pivotal role in TQ's anticancer mechanisms in breast cancer. These findings could lay the groundwork for developing future TQ-based therapies.
Insights
Thymoquinone (TQ) inhibits breast cancer cell growth by altering protein levels, particularly affecting metabolism and protein synthesis pathways. This study reveals new molecular targets for TQ-based cancer therapies.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Thymoquinone (TQ) exhibits antitumorigenic properties in breast cancer.
- The precise molecular mechanisms underlying TQ's antiproliferative effects are not fully understood.
- Investigating proteome-level changes can elucidate TQ's impact on cellular pathways.
Purpose of the Study:
- To investigate the molecular mechanisms of Thymoquinone's (TQ) antiproliferative effects in breast cancer.
- To analyze proteome-wide changes induced by TQ treatment in MCF-7 cells.
- To identify novel molecular targets and pathways affected by TQ.
Main Methods:
- MCF-7 cells were treated with Thymoquinone (TQ) at its inhibitory concentration (IC50).
- Proteomic analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- Bioinformatic tools, including Cytoscape, were used for protein annotation and hub protein identification; Western blot validated findings.
Main Results:
- Label-free quantitation identified 629 master proteins, with 104 upregulated and 477 downregulated.
- 150 proteins exhibited significant regulation, with ribosomal proteins identified as central.
- TQ significantly impacted carbon metabolism, amino acid biosynthesis, protein synthesis, and the citrate cycle, indicating metabolic reprogramming.
Conclusions:
- Thymoquinone (TQ) exerts antiproliferative effects in breast cancer by modulating key metabolic pathways and protein synthesis.
- This study identifies novel molecular targets involved in metabolic reprogramming, crucial for TQ's anticancer activity.
- The findings provide a foundation for developing novel Thymoquinone-based breast cancer therapies.
