Telomerase inhibition

Shammas M.A., Simmons C.G., Corey D.R., Reis R.J.S. Telomerase inhibition by peptide nucleic acids reverses immortality of transformed human cells. Oncogene 1999 18 6191-6200... 

NAASANI I, SEIMIYA H and TSURUO T (1998) Telomerase inhibition, telomere shortening, and senescence of cancer cells by tea catechins , Biochem Biophys Res Commun, 249 (2), 391-6. 

Chen Z, Koeneman KS, Corey DR (2003) Consequences of telomerase inhibition and combination treatments for the proliferation of cancer cells. Cancer Res 63(18) 5917-... 

Perry PJ et al. (1998) Human telomerase inhibition by regioisomeric disubstituted amidoanthracene-9,10-diones. J Med Chem 41(24) 4873-4884... 

Harrison RJ et al. (1999) Human telomerase inhibition by substituted acridine derivatives. Bioorg Med Chem Lett 9(17) 2463-2468... 

Fedoroff OY et al. (1998) NMR-based model of a telomerase-inhibiting compoimd bound to G-quadruplex DNA. Biochemistry 37(36) 12367-12374... 

Ogretmen, B., J. M. Kraveka, D. Schady, J. Usta, Y. A. Hannun, and L. M. Obeid. 2001. Molecular mechanisms of ceramide-mediated telomerase inhibition in the A549 human lung adenocarcinoma cell line. J Biol Chem 276(35) 32506-14. 

Shammas MA, Reis RJS, Cheng L, Koley H, Hurley LH, Anedrson KC, Munshi NC (2004) Telomerase inhibition and cell growth arrest after telomestatin treatment in multiple myeloma. Chn Cancer Res... 

Pascolo E, Wenz C, Lingner J et al. Mechanism of human telomerase inhibition by BIBR1532, a synthetic, non- nucleosidic drug candidate. J.Biol.Chem. 2002 277 15566-15572. 

Scheme 7 Steps involved in the synthesis of a new series of quindoline derivatives (1-10) that yield potent telomerase inhibition [31]...

Cunningham AP et al. (2006) Telomerase inhibition in cancer therapeutics molecular-based approaches. Curr Med Chem 13(24) 2875-2888... 

Several unusual polysaccharides have been isolated from sponges (11), among which the most unusual is axinelloside A (149), which has been isolated recently as a potent telomerase inhibiter imm Axinella infundibula (12). It resembles bacterial lipopoly saccharides. 

Corey DR. 2002. Telomerase inhibition, oligonucleotides, and clinical trials. Oncogene 21 631-37... 

Verbascoside is able to inhibit another enzyme related to tumor cells, the telomerase [85]. The tumoral cells express this enzyme that elongates the 3 ends of telomere [133]. Telomere shortening and telomerase activity have been detected in almost all human tumors but not in normal somatic tissues [133, 134], Zhang and cols, [85] showed that the telomerase inhibition by verbascoside may involve telomere-lenght regulation. 

Although verbascoside can arrest tumor cell growth, repair DNA oxidative damage and induce cell apoptosis and differentiation, whether telomerase inhibition by verbascoside may lead to tumor cell apoptosis, and whether all the cell cycle changes exist as a common mechanism, is not yet known. 

It was also observed earlier that G-quadruplex ligands indueed more rapid effects on cell growth than that initially expected for telomerase inhibition alone. Apoptosis and short-term response were observed with triazine derivatives (12459, 115405), telomestatin, and more recently with the pyridine dicarboxamide derivatives (307A, 360A). " Telomestatin induced the activation of ATM and Chk2 that corresponded to an activation of the DNA damage response. 12459 induced apoptosis through the mitochondrial pathway and also provoked the early activation of P53. ... 

Geron (Menlo Park, CA) Human stem cells for range, of disorders, telomerase inhibition cloning Telomerase inhibitors for cancer telomerized cells for research (preclinical)... 

Telomerase Inhibition Strategies and Protocols, edited by Lucy Andrews and Trygve O. Tollefsbol, 2007... 

Telomerase Telomerase activity is one of the most important factors that have been linked to multiple developmental processes, including cell proliferation, differentiation, aging, and senescence. Dysregulation of telomerase has often been found in developmental abnormalities and cancer, where telomere dysfunction leads to an increase in initiation of tumor lesions, due to enhanced genomic instability. Recently, a number of studies have described pol)q)henol effects on telomerase inhibition. Naasani et al. reported that EGCG directly in-... 

An important prediction is the expectation of a delay in the actions of telomerase inhibitors. Because sufficient telomere shortening needs to occur for senescence and crisis to be induced, the effects of telomerase inhibition will be observed only after the treated cancer cells have done sufficient number of cell divisions [2, 37]. Because of their delayed action, telomerase inhibitors are not going to be useful as a primary line of treatment. But to block the regrowth of residual disease after standard therapy, these inhibitors should be most valuable (Fig. 2). To produce recurrent tumors, surviving cancer cells need to undergo massive numbers of cell divisions. In the presence of a telomerase inhibitor, the... 

Because sufficient telomere attrition needs to occur before telomerase-inhibited cancer cells reach crisis, the effects of telomerase inhibitors will be delayed until the target cells have done sufficient numbers of cell divisions. This delay, which may preclude their use as a first line of treatment, should not reduce the ability of these compounds to block the regrowth of residual disease. After conventional therapy, telomerase inhibitors could be used to reduce the incidence of recurrences and promote long-term survival... 

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