title: Glucose restriction decreases telomerase activity and enhances its inhibitor response on breast cancer cells: possible extra-telomerase role of BIBR 1532.
abstract: BACKGROUND
  Considerable progress has been made to understand the association between lifestyle and diet in cancer initiation and promotion. Because excessive glucose consumption is a key metabolic hallmark of cancer cells, glucose restriction (GR) decreases the proliferation, and promotes the differentiation and transformation of cancer cells to quiescent cells. The immortality of cancerous cells is largely assured by telomerase, which is an interesting target for inhibition by BIBR 1532. In this study, we investigated the effect of GR on telomerase activity and on the efficacy of its inhibition by BIBR 1532.
  
  
  METHODS
  Breast cancer MDA-MB 231 and MCF-7 cells were cultured in DMEM (Dulbecco's modified eagle's media) with 0, 1 or 4.5 g/l of glucose. The telomerase activity was measured via quantitative Real-Time PCR, and the two telomerase subunits were semi-quantified by RT-PCR. Proliferation test and mitochondrial metabolism were assessed via tetrazolium salt reduction and cell counts; apoptosis was assessed via caspase-3 quantification and flow cytometry.
  
  
  RESULTS
  A decrease in the telomerase activity of more than 75% was associated with a significant reduction in the mRNA expression of its catalytic subunit hTERT (Reverse Transcriptase) and a decrease in the mitochondrial metabolism by more than 80% under restricted glucose conditions. In addition, GR increased the effect of BIBR 1532. Glucose deprivation induces apoptosis via BIBR 1532-mediated telomerase inhibition in triple negative breast cancer cells, as assessed by caspase-3 measurements and Annexin analysis.
  
  
  CONCLUSIONS
  Taken together, our results suggest that the effect of BIBR 1532 is potentiated by GR to induce triple negative breast cancer cell death.
authors.affiliation: Cancer and Metabolism Laboratory, Faculty of Medicine, Campus of Medical Sciences, Saint-Joseph University, Damascus Road, P.O.Box 11-5076, Riad el Solh, Beirut 1107 2180, Lebanon.
authors.forename: Layal
authors.initials: L
authors.lastname: Wardi
authors.affiliation: Regenerative Medicine Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon.
authors.forename: Nada
authors.initials: N
authors.lastname: Alaaeddine
authors.affiliation: Department of Infectious Diseases, the University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Issam
authors.initials: I
authors.lastname: Raad
authors.affiliation: Surgery Department, Faculty of Medicine, Saint-Joseph University and Hotel-Dieu de France, Beirut, Lebanon.
authors.forename: Riad
authors.initials: R
authors.lastname: Sarkis
authors.affiliation: Regenerative Medicine Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon.
authors.forename: Rim
authors.initials: R
authors.lastname: Serhal
authors.affiliation: Regenerative Medicine Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon.
authors.forename: Charbel
authors.initials: C
authors.lastname: Khalil
authors.affiliation: Cancer and Metabolism Laboratory, Faculty of Medicine, Campus of Medical Sciences, Saint-Joseph University, Damascus Road, P.O.Box 11-5076, Riad el Solh, Beirut 1107 2180, Lebanon.
authors.forename: George
authors.initials: G
authors.lastname: Hilal
keywords: BIBR 1532; Breast cancer; Cancer; Glucose restriction; Telomerase
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