The Relationship Between The Usage of Telomerase Inhibitor BIBR1532 and Autophagy in Breast Cancer Stem Cells
Project no. 32941 · Status: Kapanmış (Yayın bekleniyor) · 2025
Summary
<p>Breast cancer stem cells play a pivotal role in tumor progression, therapeutic resistance, and disease recurrence owing to their intrinsic self-renewal and tumor-initiating capabilities. This study investigated the molecular effects of BIBR1532, a selective telomerase inhibitor, on cell viability, apoptotic pathways, and autophagy-related processes in breast cancer stem cells. Human breast cancer stem cells were maintained in culture, where optimal cell density was defined via proliferation assays, and the cytotoxic efficacy of BIBR1532 was quantitatively evaluated using the WST-1 assay. Following a 48-hour treatment period, the $IC_{50}$ value was determined to be 29.91 µM, while apoptotic rates were analyzed using Annexin V/PI double staining combined with flow cytometry. Expression alterations across autophagyassociated genes were profiled using an RT-qPCR array. Among 54 genes exhibiting statistically significant modulation, 39 genes of the Array were up-regulated and 15 genes of the array were down-regulated. Specifically, transcriptional levels of SQSTM1/p62, ULK2, TP53, MAPK14/p38α, and UVRAG were elevated, whereas AKT1, PIK3C3, RPS6KB1/S6K, and ATG7 were suppressed. Analysis highlighted a pronounced pathway enrichment related to autophagy, apoptosis, and mitophagy. Overall, these findings indicate that while BIBR1532 promotes apoptotic cell death, it induces an impaired or incomplete autophagic cascade rather than full autophagic activation. These insights contribute to deciphering the interplay between telomerase inhibition and autophagy, serving as a basis for novel targeted or combination therapeutic paradigms in breast cancer. </p>