Glucose restriction decreases telomerase activity and enhances its inhibitor response on breast cancer cells: possible extra-telomerase role of BIBR 1532
Background
Significant progress has been made in understanding the relationship between lifestyle, diet, and cancer development. Since excessive glucose consumption is a hallmark of cancer metabolism, glucose restriction (GR) can reduce proliferation and promote the transformation of cancer cells into a quiescent state. Telomerase, a key enzyme responsible for cellular immortality in cancer, represents an attractive target for inhibition by BIBR 1532. This study examines the impact of GR on telomerase activity and its sensitivity to inhibition by BIBR 1532.
Methods
MDA-MB-231 and MCF-7 breast cancer cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) containing 0, 1, or 4.5 g/L of glucose. Telomerase activity was measured using quantitative real-time PCR, while its two subunits were semi-quantified via RT-PCR. Cell proliferation and mitochondrial metabolism were assessed using tetrazolium salt reduction assays and cell counts. Apoptosis was evaluated through caspase-3 quantification and flow cytometry.
Results
Under glucose restriction, telomerase activity decreased by more than 75%, accompanied by a significant reduction in hTERT (telomerase reverse transcriptase) mRNA expression and an over 80% decline in mitochondrial metabolism. Additionally, GR enhanced the efficacy of BIBR 1532, leading to increased apoptosis in triple-negative breast cancer cells, as demonstrated by caspase-3 activation and Annexin V staining.
Conclusions
These findings suggest that glucose restriction enhances the anti-telomerase effect of BIBR 1532, effectively promoting apoptosis in triple-negative breast cancer cells.