The impact of the telomerase inhibitor on the Wnt signaling pathway in breast cancer and breast cancer stem cells.
Breast cancer remains one of the leading causes of cancer-related mortality in women worldwide. Breast cancer stem cells (BCSCs) contribute to tumor initiation, metastasis, recurrence, and resistance to therapy. The Wnt signaling pathway is a major regulator of stemness properties and is associated with poor clinical outcomes. BIBR1532 is a selective telomerase inhibitor widely used in cancer research due to its ability to inhibit telomerase activity in tumor cells with minimal toxicity in normal tissues. This study aimed to investigate the effects of BIBR1532 on the Wnt signaling pathway in breast cancer cells and BCSCs.
Cytotoxicity of BIBR1532 was evaluated in MCF-7 breast cancer cells, MCF10A normal breast epithelial cells, and BCSCs using a 48-hour treatment. IC₅₀ values were calculated, and apoptosis induction was assessed. Changes in the expression of Wnt pathway-related genes following BIBR1532 treatment were analyzed using RT-qPCR.
The IC₅₀ values of BIBR1532 at 48 h were 35.29 µM for MCF-7, 28.16 µM for MCF10A, and 30.42 µM for the BCSC line. BIBR1532 markedly induced apoptosis in MCF-7 and BCSCs, whereas minimal apoptotic changes were observed in MCF10A cells. RT-qPCR analysis revealed significant modulation of genes in the Wnt signaling pathway: several oncogenic components were downregulated, while multiple tumor-suppressive genes were upregulated. Additionally, expression changes in less-studied Wnt-related genes may provide new insights for future breast cancer research.
BIBR1532 exerts selective cytotoxic and pro-apoptotic effects on breast cancer cells and BCSCs and modulates key components of the Wnt signaling pathway. These findings suggest that telomerase inhibition may influence stemness-related signaling in breast cancer.
Cytotoxicity of BIBR1532 was evaluated in MCF-7 breast cancer cells, MCF10A normal breast epithelial cells, and BCSCs using a 48-hour treatment. IC₅₀ values were calculated, and apoptosis induction was assessed. Changes in the expression of Wnt pathway-related genes following BIBR1532 treatment were analyzed using RT-qPCR.
The IC₅₀ values of BIBR1532 at 48 h were 35.29 µM for MCF-7, 28.16 µM for MCF10A, and 30.42 µM for the BCSC line. BIBR1532 markedly induced apoptosis in MCF-7 and BCSCs, whereas minimal apoptotic changes were observed in MCF10A cells. RT-qPCR analysis revealed significant modulation of genes in the Wnt signaling pathway: several oncogenic components were downregulated, while multiple tumor-suppressive genes were upregulated. Additionally, expression changes in less-studied Wnt-related genes may provide new insights for future breast cancer research.
BIBR1532 exerts selective cytotoxic and pro-apoptotic effects on breast cancer cells and BCSCs and modulates key components of the Wnt signaling pathway. These findings suggest that telomerase inhibition may influence stemness-related signaling in breast cancer.
Authors
Guler Guler, Sabour Takanlou Sabour Takanlou, Sabour Takanlou Sabour Takanlou, Rostamlou Rostamlou, Biray Avci Biray Avci
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