1.Critical Role for Telomerase in the Mechanism of Flow-Mediated Dilation in the Human Microcirculation.
Beyer AM1, Freed JK2, Durand MJ2, Riedel M2, Ait-Aissa K2, Green P2, Hockenberry JC2, Morgan RG2, Donato AJ2, Peleg R2, Gasparri M2, Rokkas CK2, Santos JH2, Priel E2, Gutterman DD2. Circ Res. 2016 Mar 4;118(5):856-66. doi: 10.1161/CIRCRESAHA.115.307918. Epub 2015 Dec 23.
RATIONALE: Telomerase is a nuclear regulator of telomere elongation with recent reports suggesting a role in regulation of mitochondrial reactive oxygen species. Flow-mediated dilation in patients with cardiovascular disease is dependent on the formation of reactive oxygen species.
2.Targeted inhibition of telomerase activity combined with chemotherapy demonstrates synergy in eliminating ovarian cancer spheroid-forming cells.
Meng E1, Taylor B, Ray A, Shevde LA, Rocconi RP. Gynecol Oncol. 2012 Mar;124(3):598-605. doi: 10.1016/j.ygyno.2011.11.018. Epub 2011 Nov 22.
OBJECTIVE: Telomerase activity (TA) is often used as a molecular marker for cancer aggressiveness. Our objectives were to determine the TA in ovarian cancer cell lines and the effectiveness of targeting telomerase for cancer therapy.
3.Telomerase inhibition by non-nucleosidic compound BIBR1532 causes rapid cell death in pre-B acute lymphoblastic leukemia cells.
Bashash D1, Ghaffari SH, Mirzaee R, Alimoghaddam K, Ghavamzadeh A. Leuk Lymphoma. 2013 Mar;54(3):561-8. doi: 10.3109/10428194.2012.704034. Epub 2012 Sep 28.
Since unlimited proliferative potential has been identified as a major and, to date, therapeutically unexploited phenotypic hallmark of cancer, telomere maintenance mechanisms have been proposed as potential targets for new anticancer interventions. This study was aimed to investigate the effects of BIBR1532, the lead compound of non-nucleosidic inhibition of telomerase, on pre-B acute lymphoblastic leukemia (ALL) cells. BIBR1532 caused rapid cell death in Nalm-6 cells probably through transcriptional suppression of survivin-mediated c-Myc and human telomerase reverse transcriptase (hTERT) expression in a concentration-dependent manner. Moreover, our results also suggest that induced p73, up-regulated Bax/Bcl-2 molecular ratio and subsequent activation of caspase-3 may contribute to a direct short-term cytotoxic effect of high doses of BIBR1532, independent of long-term substantial telomere erosion-mediated cell cycle arrest.
4.Glucose restriction decreases telomerase activity and enhances its inhibitor response on breast cancer cells: possible extra-telomerase role of BIBR 1532.
Wardi L1, Alaaeddine N2, Raad I3, Sarkis R4, Serhal R2, Khalil C2, Hilal G1. Cancer Cell Int. 2014 Jul 4;14:60. doi: 10.1186/1475-2867-14-60. eCollection 2014.
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.