A novel chromen-based small molecule induces apoptosis and modulates cellular response to triple-negative breast
Bernardine Tuah1,2,3, Kwadwo Fosu1,2, Diana Ahu Prah1
1West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), College of Basic and Applied Sciences, University of Ghana, Legon, Accra, Ghana.
Abstract:
Triple-negative breast cancer (TNBC) is challenging to treat due to its aggressive nature. Its lack of hormone receptors renders conventional therapies less effective. This study assessed the efficacy of a novel compound, compound 2, in modulating TNBC cell behaviour. We used in vitro assays with MDA-MB-468 and MDA-MB-231 cell lines. Methods included annexin V apoptosis assay, flow cytometry for cell cycle and qRT-PCR for gene expression. Clonogenic, adhesion and wound healing assays were used for phenotypic characterization. Cytokine and chemokine levels in MDA-MB-468 cells were also measured using a Luminex assay. Compound 2 increased both early and late apoptosis in cancer cells, particularly MDA MB 468 cells. It also upregulated pro-apoptotic genes while downregulating anti-apoptotic genes. Additionally, it induced G1-phase arrest in MDA MB 468 cells with downregulation in Ki67 expression. Compound 2 also reduced cancer stem cell populations, suppressed colony formation, and impaired cell migration at IC50 concentrations. Significant changes in gene expression profiles for EMT-related genes were observed. Compound 2 decreased IL4 and IL8 levels and increased CCL2 and CXCL1. However, it did not significantly affect the levels of IL6, IL10, CXCL2, CCL5, TNF-α, IFN-γ, IL-1β, and IL2. Compound 2 thus exhibited a multifaceted anticancer profile, suggesting its potential in preventing cancer relapse and limiting cell proliferation which makes it a promising candidate for TNBC targeted therapy. This study lays the groundwork for further in vivo studies and potential clinical applications to explore full therapeutic potential of compound 2 in aggressive breast cancer types.
Insights
A novel compound, compound 2, shows promise for treating triple-negative breast cancer (TNBC). It effectively induces cancer cell death, halts proliferation, and inhibits metastasis, offering a potential new targeted therapy for this aggressive disease.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) presents a significant therapeutic challenge due to its aggressive nature and lack of hormone receptors, limiting conventional treatment efficacy.
- Novel therapeutic strategies are urgently needed to target TNBC's unique biological characteristics and improve patient outcomes.
Purpose of the Study:
- To evaluate the efficacy of a novel compound, compound 2, in modulating the behavior of triple-negative breast cancer cells.
- To investigate the mechanisms by which compound 2 exerts its anti-cancer effects in vitro.
Main Methods:
- In vitro assays using MDA-MB-468 and MDA-MB-231 TNBC cell lines.
- Annexin V apoptosis assay, cell cycle analysis via flow cytometry, and quantitative real-time PCR (qRT-PCR) for gene expression.
- Clonogenic, adhesion, wound healing, and Luminex assays for phenotypic characterization and cytokine/chemokine profiling.
Main Results:
- Compound 2 significantly increased apoptosis, induced G1-phase cell cycle arrest, and downregulated Ki67 expression in TNBC cells.
- It suppressed cancer stem cell populations, colony formation, and cell migration, while altering gene expression related to epithelial-mesenchymal transition (EMT).
- Compound 2 modulated specific cytokine and chemokine levels, including decreased IL4/IL8 and increased CCL2/CXCL1.
Conclusions:
- Compound 2 demonstrates a multifaceted anti-cancer profile against TNBC, including induction of apoptosis, cell cycle arrest, and inhibition of key cancer hallmarks.
- Its ability to reduce cancer stemness and migration suggests potential in preventing relapse and limiting proliferation.
- Compound 2 represents a promising candidate for targeted TNBC therapy, warranting further in vivo and clinical investigation.
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