5-Azacitidine and Trichostatin A induce DNA damage and apoptotic responses in tongue squamous cell carcinoma: An in vitro study

Hodjat, Mahshid; Jourshari, Parisa Bina; Amirinia, Fatemeh; Asadi, Nasrin

doi:10.1016/j.archoralbio.2021.105296

Cited by 4 publications

(1 citation statement)

References 30 publications

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“…Human cells are constantly exposed to different DNA-damaging factors, both exogenous and endogenous, that induce DSBs ( Figure 1 ) and respond to the onset of damage by H2AX phosphorylation and the activation of the repair pathway [ 17 ]. Exogenous factors are represented by environmental and clinical factors including background radiation, radiation accidents, occupational exposure, chemical mutagens, heat, medical IR exposure, and chemotherapeutic drugs [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Endogenous factors include genome rearrangements such as V(D)J recombination or meiotic recombination, free radicals produced during oxidative stress, telomere shortening in senescent cells, DNA fragmentation during apoptosis, and hypoxia [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ].…”

Section: Basic Mechanism Of H2ax Phosphorylationmentioning

confidence: 99%

Factors to Consider for the Correct Use of γH2AX in the Evaluation of DNA Double-Strand Breaks Damage Caused by Ionizing Radiation

Valente

Gentileschi

Guerrisi

et al. 2022

Cancers

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People exposed to ionizing radiation (IR) both for diagnostic and therapeutic purposes is constantly increasing. Since the use of IR involves a risk of harmful effects, such as the DNA DSB induction, an accurate determination of this induced DNA damage and a correct evaluation of the risk–benefit ratio in the clinical field are of key relevance. γH2AX (the phosphorylated form of the histone variant H2AX) is a very early marker of DSBs that can be induced both in physiological conditions, such as in the absence of specific external agents, and by external factors such as smoking, heat, background environmental radiation, and drugs. All these internal and external conditions result in a basal level of γH2AX which must be considered for the correct assessment of the DSBs after IR exposure. In this review we analyze the most common conditions that induce H2AX phosphorylation, including specific exogenous stimuli, cellular states, basic environmental factors, and lifestyles. Moreover, we discuss the most widely used methods for γH2AX determination and describe the principal applications of γH2AX scoring, paying particular attention to clinical studies. This knowledge will help us optimize the use of available methods in order to discern the specific γH2AX following IR-induced DSBs from the basal level of γH2AX in the cells.

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Section: Basic Mechanism Of H2ax Phosphorylationmentioning

confidence: 99%

Factors to Consider for the Correct Use of γH2AX in the Evaluation of DNA Double-Strand Breaks Damage Caused by Ionizing Radiation

Valente

Gentileschi

Guerrisi

et al. 2022

Cancers

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5-aza-2′-deoxycytidine induces telomere dysfunction in breast cancer cells

Al-dulaimi,

Matta,

Slijepcevic

et al. 2024

Biomedicine & Pharmacotherapy

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Enhanced Cytotoxic Effects in Human Oral Squamous Cell Carcinoma Cells Treated with Combined Methyltransferase Inhibitors and Histone Deacetylase Inhibitors

et al. 2022

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Combined treatment of human oral squamous cell carcinoma (OSCCs) with DNA methyltransferase inhibitors (DNMTis), histone methyltransferase inhibitors (HMTis), and histone deacetylase inhibitors (HDACis), and the molecular mechanisms underlying their anticancer effects, have not been fully elucidated. Herein, we investigated the cytotoxic effects of combined DNMTis (5-Aza-deoxycytidine: 5-Aza-dC, RG108), HMTis (3-deazaneplanocin A: DZNep), and HDACis (trichostatin A: TSA) treatment on human OSCC cells and explored their molecular mechanisms. Combined 5-Aza-dC, or RG108, and TSA treatment significantly decreased HSC-2 and Ca9-22 cell viability. Combinatorial DZNep and TSA treatment also decreased Ca9-22 cell viability. Although caspase 3/7 activation was not observed in HSC-2 cells following combined treatment, caspase activity was significantly increased in Ca9-22 cells treated with DZNep and TSA. Moreover, combined treatment with 5-Aza-dC, RG108, and TSA increased the proportion of HSC-2 and Ca9-22 cells in the S and G2/M phases. Meanwhile, increased phosphorylation of the histone variant H2A.X, a marker of double-stranded DNA breaks, was observed in both cells after combination treatment. Hence, the decreased viability induced by combined treatment with epigenomic inhibitors results from apoptosis and cell cycle arrest in S and G2/M phases. Thus, epigenomic therapy comprising combined low concentrations of DNMTi, HMTi, and HDACi is effective against OSCC.

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5-Azacitidine and Trichostatin A induce DNA damage and apoptotic responses in tongue squamous cell carcinoma: An in vitro study

Cited by 4 publications

References 30 publications

Factors to Consider for the Correct Use of γH2AX in the Evaluation of DNA Double-Strand Breaks Damage Caused by Ionizing Radiation

Factors to Consider for the Correct Use of γH2AX in the Evaluation of DNA Double-Strand Breaks Damage Caused by Ionizing Radiation

5-aza-2′-deoxycytidine induces telomere dysfunction in breast cancer cells

Enhanced Cytotoxic Effects in Human Oral Squamous Cell Carcinoma Cells Treated with Combined Methyltransferase Inhibitors and Histone Deacetylase Inhibitors

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