Phosphorothioate-modified antisense oligonucleotides against human telomerase reverse transcriptase sensitize cancer cells to radiotherapy

Cao, Fei; Ju, Xingzhu; Chen, Di; Jiang, Lingong; Zhu, Xiaofei; Qing, Shuiwang; Fang, Fang; Shen, Yao; Jia, Zhen; Zhang, Huojun

doi:10.3892/mmr.2017.6778

Cited by 10 publications

(7 citation statements)

References 23 publications

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“…These predictions need to be validated. We note here that phosphorothioate-mediated augmentation of radiation damage to cells has already been reported and has been proposed to improve the radiotherapeutic efficacy of liver cancer …”

Section: Discussionmentioning

confidence: 85%

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Modulation of the Directionality of Hole Transfer between the Base and the Sugar-Phosphate Backbone in DNA with the Number of Sulfur Atoms in the Phosphate Group

et al. 2022

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This work shows that S atom substitution in phosphate controls the directionality of hole transfer processes between the base and sugar-phosphate backbone in DNA systems. The investigation combines synthesis, electron spin resonance (ESR) studies in supercooled homogeneous solution, pulse radiolysis in aqueous solution at ambient temperature, and density functional theory (DFT) calculations of in-house synthesized model compound dimethylphosphorothioate (DMTP(O–)S) and nucleotide (5’-O-methoxyphosphorothioyl-2′-deoxyguanosine (G–P(O–)S)). ESR investigations show that DMTP(O–)S reacts with Cl2 •– to form the σ2σ*1 adduct radical −P–SCl, which subsequently reacts with DMTP(O–)S to produce [−P–SS–P−]−. −P–SCl in G–P(O–)S undergoes hole transfer to Gua, forming the cation radical (G•+) via thermally activated hopping. However, pulse radiolysis measurements show that DMTP(O–)S forms the thiyl radical (−P–S•) by one-electron oxidation, which did not produce [−P–SS–P−]−. Gua in G–P(O–)S is oxidized unimolecularly by the −P–S• intermediate in the sub-picosecond range. DFT thermochemical calculations explain the differences in ESR and pulse radiolysis results obtained at different temperatures.

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Section: Discussionmentioning

confidence: 85%

“…We note here that phosphorothioatemediated augmentation of radiation damage to cells has already been reported and has been proposed to improve the radiotherapeutic efficacy of liver cancer. 78 ■ ASSOCIATED CONTENT * sı Supporting Information…”

mentioning

confidence: 99%

Modulation of the Directionality of Hole Transfer between the Base and the Sugar-Phosphate Backbone in DNA with the Number of Sulfur Atoms in the Phosphate Group

et al. 2022

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“…DNA phosphorothioation is a fascinating phenomenon that holds high promise for potential application in gene silencing 45 and genome editing 46 , 47 . Phosphorothioated antisense oligonucleotides have also recently been used to target human telomerase for cancer therapy 48 . Our work might suggest clues for designing new generations of Cas9-like genome editing nucleases through utilizing the special PT-DNA recognition expertize of SBD domains.…”

Section: Discussionmentioning

confidence: 99%

Structural basis for the recognition of sulfur in phosphorothioated DNA

Guang

Zhang

et al. 2018

Nat Commun

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There have been very few reports on protein domains that specifically recognize sulfur. Here we present the crystal structure of the sulfur-binding domain (SBD) from the DNA phosphorothioation (PT)-dependent restriction endonuclease ScoMcrA. SBD contains a hydrophobic surface cavity that is formed by the aromatic ring of Y164, the pyrolidine ring of P165, and the non-polar side chains of four other residues that serve as lid, base, and wall of the cavity. The SBD and PT-DNA undergo conformational changes upon binding. The S187RGRR191 loop inserts into the DNA major groove to make contacts with the bases of the GPSGCC core sequence. Mutating key residues of SBD impairs PT-DNA association. More than 1000 sequenced microbial species from fourteen phyla contain SBD homologs. We show that three of these homologs bind PT-DNA in vitro and restrict PT-DNA gene transfer in vivo. These results show that SBD-like PT-DNA readers exist widely in prokaryotes.

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“…siRNAs can be used for silencing the genes that contribute to radioresistance. An antisense oligonucleotide against telomerase reverse transcriptase is an example of the radiosensitizing function of oligonucleotides 78 . Knockdown of survivin by siRNA negatively modulated the inhibition of caspase activation, leading to increased apoptosis after RT 79 .…”

Section: Radiosensitizing Agentsmentioning

confidence: 99%

Application of nano‐radiosensitizers in combination cancer therapy

Varzandeh

Sabouri

Mansouri

et al. 2023

Bioengineering & Transla Med

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Radiosensitizers are compounds or nanostructures, which can improve the efficiency of ionizing radiation to kill cells. Radiosensitization increases the susceptibility of cancer cells to radiation‐induced killing, while simultaneously reducing the potentially damaging effect on the cellular structure and function of the surrounding healthy tissues. Therefore, radiosensitizers are therapeutic agents used to boost the effectiveness of radiation treatment. The complexity and heterogeneity of cancer, and the multifactorial nature of its pathophysiology has led to many approaches to treatment. The effectiveness of each approach has been proven to some extent, but no definitive treatment to eradicate cancer has been discovered. The current review discusses a broad range of nano‐radiosensitizers, summarizing possible combinations of radiosensitizing NPs with several other types of cancer therapy options, focusing on the benefits and drawbacks, challenges, and future prospects.

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Phosphorothioate-modified antisense oligonucleotides against human telomerase reverse transcriptase sensitize cancer cells to radiotherapy

Cited by 10 publications

References 23 publications

Modulation of the Directionality of Hole Transfer between the Base and the Sugar-Phosphate Backbone in DNA with the Number of Sulfur Atoms in the Phosphate Group

Modulation of the Directionality of Hole Transfer between the Base and the Sugar-Phosphate Backbone in DNA with the Number of Sulfur Atoms in the Phosphate Group

Structural basis for the recognition of sulfur in phosphorothioated DNA

Application of nano‐radiosensitizers in combination cancer therapy

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