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Thymoquinone Inhibition of Chemokines in TNF-α-Induced Inflammatory and Metastatic Effects in Triple-Negative Breast
Getinet M Adinew1, Samia Messeha1, Equar Taka1
1Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL 32307, USA.
Abstract:
The lack of identifiable molecular targets or biomarkers hinders the development of treatment options in triple-negative breast cancer (TNBC). However, natural products offer a promising alternative by targeting inflammatory chemokines in the tumor microenvironment (TME). Chemokines are crucial in promoting breast cancer growth and metastasis and correlate to the altered inflammatory process. In the present study, we evaluated the anti-inflammatory and antimetastatic effects of the natural product thymoquinone (TQ) on TNF-α-stimulated TNBC cells (MDA-MB-231 and MDA-MB-468) to study the cytotoxic, antiproliferative, anticolony, antimigratory, and antichemokine effects using enzyme-linked immunosorbent assays, quantitative real-time reverse transcription-polymerase chain reactions, and Western blots were used in sequence to validate the microarray results further. Four downregulated inflammatory cytokines were identified, CCL2 and CCL20 in MDA-MB-468 cells and CCL3 and CCL4 in MDA-MB-231 cells. Furthermore, when TNF-α-stimulated MDA-MB-231 cells were compared with MDA-MB-468 cells, the two cells were sensitive to TQ's antichemokine and antimetastatic effect in preventing cell migration. It was concluded from this investigation that genetically different cell lines may respond to TQ differently, as TQ targets CCL3 and CCL4 in MDA-MB-231 cells and CCL2 and CCL20 in MDA-MB-468 cells. Therefore, the results indicate that TQ may be recommended as a component of the therapeutic strategy for TNBC treatment. These outcomes stem from the compound's capacity to suppress the chemokine. Even though these findings support the usage of TQ as part of a therapy strategy for TNBC associated with the identified chemokine dysregulations, additional in vivo studies are needed to confirm these in vitro results.
Insights
Thymoquinone (TQ), a natural product, shows promise in treating triple-negative breast cancer (TNBC) by reducing inflammatory chemokines that drive cancer growth and metastasis. Further research is needed to confirm these findings in vivo.
Area of Science:
- Oncology
- Natural Products Chemistry
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) lacks specific molecular targets, necessitating novel therapeutic strategies.
- Natural products, like thymoquinone (TQ), show potential by targeting inflammatory chemokines within the tumor microenvironment (TME).
- Chemokines play a critical role in breast cancer progression and metastasis, correlating with inflammatory processes.
Purpose of the Study:
- To evaluate the anti-inflammatory and antimetastatic effects of thymoquinone (TQ) on tumor necrosis factor-alpha (TNF-α)-stimulated TNBC cells.
- To investigate the impact of TQ on TNBC cell cytotoxicity, proliferation, colony formation, migration, and chemokine expression.
- To identify specific chemokine targets of TQ in different TNBC cell lines.
Main Methods:
- Utilized enzyme-linked immunosorbent assays (ELISAs), quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), and Western blotting.
- Assessed cytotoxic, antiproliferative, anticolony, and antimigratory effects of TQ.
- Validated microarray findings by quantifying inflammatory cytokine expression.
Main Results:
- TQ demonstrated cytotoxic, antiproliferative, anticolony, and antimigratory effects on TNF-α-stimulated TNBC cells (MDA-MB-231 and MDA-MB-468).
- Identified downregulated inflammatory cytokines: CCL2 and CCL20 in MDA-MB-468 cells; CCL3 and CCL4 in MDA-MB-231 cells.
- Both cell lines showed sensitivity to TQ's antichemokine and antimetastatic effects, particularly in inhibiting cell migration.
Conclusions:
- Thymoquinone (TQ) exhibits significant anti-inflammatory and antimetastatic properties against TNBC.
- TQ's therapeutic efficacy varies between genetically distinct TNBC cell lines, targeting specific chemokines (CCL3/CCL4 in MDA-MB-231; CCL2/CCL20 in MDA-MB-468).
- TQ is a potential therapeutic agent for TNBC, warranting further in vivo investigation to confirm its role in chemokine-targeted therapy.
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