Alternative telomere-lengthening mechanisms

Grach, Andrey

doi:10.3103/s0095452711020046

Cited by 2 publications

(2 citation statements)

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“…Second, telomerase-mediated telomere elongation is not the only mechanism involved in tumorigenesis. In a small number of human tumors, telomerase shortening caused by long-term and low-dose treatment with telomerase inhibitors can be compensated by activation of alternative lengthening of telomere (ALT) [14][15][16]. It is clear that time and dose are important factors influencing the efficacy of telomerase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Zeolitic Imidazolate Framework-8 (ZIF-8) as a Drug Delivery Vehicle for the Transport and Release of Telomerase Inhibitor BIBR 1532

Zhang

Lan

et al. 2023

Nanomaterials

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Telomerase is constitutively overexpressed in the majority of human cancers and telomerase inhibition provides a promising broad-spectrum anticancer therapeutic strategy. BIBR 1532 is a well-known synthetic telomerase inhibitor that blocks the enzymatic activity of hTERT, the catalytic subunit of telomerase. However, water insolubility of BIBR 1532 leads to low cellular uptake and inadequate delivery and thus, limits its anti-tumor effects. Zeolitic imidazolate framework-8 (ZIF-8) is considered as an attractive drug delivery vehicle for improved transport, release and anti-tumor effects of BIBR 1532. Herein, ZIF-8 and BIBR 1532@ZIF-8 were synthesized, respectively, and the physicochemical characterizations confirmed the successful encapsulation of BIBR 1532 in ZIF-8 coupled with an improved stability of BIBR 1532. ZIF-8 could alter the permeability of lysosomal membrane probably by the imidazole ring-dependent protonation. Moreover, ZIF-8 encapsulation facilitated the cellular uptake and release of BIBR 1532 with more accumulation in the nucleus. BIBR 1532 encapsulation with ZIF-8 triggered a more obvious growth inhibition of cancer cells as compared with free BIBR 1532. A more potent inhibition on hTERT mRNA expression, aggravated G0/G1 arrest accompanied with an increased cellular senescence were detected in BIBR 1532@ZIF-8-treated cancer cells. Our work has provided preliminary information on improving the transport, release and efficacy of water-insoluble small molecule drugs by using ZIF-8 as a delivery vehicle.

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Section: Introductionmentioning

confidence: 99%

Zeolitic Imidazolate Framework-8 (ZIF-8) as a Drug Delivery Vehicle for the Transport and Release of Telomerase Inhibitor BIBR 1532

Zhang

Lan

et al. 2023

Nanomaterials

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“…As a result, the telomere ends gain the same structure as they had prior to the telomerase action but they become much longer in this case (Blackburn & Collins, 2011;Dong et al, 2005;Testorelli, 2003). The second mechanism, which is found in a minority of neoplasm types, is accomplished by recombination-mediated telomere replication and belongs to the alternative lengthening of telomeres mechanisms (ALT) (Grach, 2011a;Grach, 2011b;Henson et al, 2002;Muntoni & Reddel, 2005;Stewart, 2005). Besides the elongation of telomeres in tumour cells, telomerase also has a high activity in stem and germ cells, thereby providing them a high proliferative capacity (Meeker & Coffey, 1997).…”

Section: Introductionmentioning

confidence: 99%

Telomere Shortening Mechanisms

Grach¹

2013

The Mechanisms of DNA Replication

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Alternative telomere-lengthening mechanisms

Cited by 2 publications

References 86 publications

Zeolitic Imidazolate Framework-8 (ZIF-8) as a Drug Delivery Vehicle for the Transport and Release of Telomerase Inhibitor BIBR 1532

Zeolitic Imidazolate Framework-8 (ZIF-8) as a Drug Delivery Vehicle for the Transport and Release of Telomerase Inhibitor BIBR 1532

Telomere Shortening Mechanisms

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