Sodium glycididazole enhances the radiosensitivity of laryngeal cancer cells through downregulation of ATM signaling pathway

Zeng, Yicheng; Xing, Rui; Zeng, Jing; Ming, Xue; Chi, Feng; Guo, Fan; Wang, Hong Mei; Duan, Qiong; Sun, Yu; Niu, Nan; Wu, Rong

doi:10.1007/s13277-015-4278-1

Cited by 10 publications

(12 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the enhancement of radiation-induced cell death by glycididazole was observed even in normoxia. A recent report by Zeng et al demonstrated the similar effect of glycididazole on normoxic laryngeal cancer cells and revealed significant downregulation of ataxia-telangiectasia mutated (ATM), p-ATM, CHK2, and p53 and the upregulation of MDM2 and Cdk2 after the combined treatment with glycididazole and X-irradiation, not only in hypoxic conditions, but also in normoxic conditions, and concluded that glycididazole has the potential to inhibit the ATM signaling response after X-irradiation (20). Although glycididazole is composed of a metronidazole dimer, to the best of our knowledge, there are no reports to demonstrate that metronidazole exerted radiation modifying effects, except for its oxygen-mimetic properties owing to the electron affinity.…”

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Preclinical study on hypoxic radiosensitizing effects of glycididazole in comparison with those of doranidazole inï¿½vitro and inï¿½vivo

et al. 2017

View full text Add to dashboard Cite

Abstract.To overcome the radioresistance of hypoxic cells in solid tumor, numerous types of radiosensitizers specifically against them have been developed. Glycididazole has a chemical structure in which two metronidazole forms are combined, and is widely used as a hypoxic radiosensitizer in China. However, a detailed investigation of its radiosensitizing properties has not been performed. The present study reported a comparative assessment of glycididazole and doranidazole, another hypoxic radiosensitizer. All experiments were performed using the murine squamous cell carcinoma cell line SCCVII. Prior to X-irradiation, the cells were treated with the test drugs at concentrations of 10 mM and 200 mg/kg in vitro and in vivo, respectively. Uptake and their intratumor chemical forms were analyzed by high performance liquid chromatography (HPLC). Both drugs enhanced the reproductive cell death induced by X-irradiation under hypoxia. However, the growth delay assay of the transplanted tumor revealed the combination of X-irradiation and glycididazole showed a similar antitumor effect to that of X-irradiation alone, whereas doranidazole significantly sensitized the cells to X-irradiation. HPLC analysis revealed that incorporated glycididazole was decomposed to metronidazole and was therefore present at a lower concentration compared with that of doranidazole. The decomposition of glycididazole to metronidazole reduced its radiosensitizing efficiency in vivo. Elucidation of the kinetics of drugs containing metabolizable chemical forms is necessary for the optimization of clinical treatment.

show abstract

Section: Discussionmentioning

confidence: 94%

“…3). Only one study has examined the antitumor effect of glycididazole using the growth delay assay in a transplanted tumor model (20). The authors demonstrated the significant radiosensitizing potential of glycididazole in a xenografted Hep-2 tumor mouse model, but they employed a high dose of glycididazole (3x700 mg/m 2 /day).…”

Section: Discussionmentioning

confidence: 99%

Preclinical study on hypoxic radiosensitizing effects of glycididazole in comparison with those of doranidazole inï¿½vitro and inï¿½vivo

et al. 2017

View full text Add to dashboard Cite

show abstract

“…While, miR-30a expression can increase IR-induced apoptosis and decrease IR-induced G2/M cell cycle arrest after 8 Gy IR. In response to IR induced DNA damage, phosphorylation of ATM can increase p53, either inducing DNA repair, cell cycle arrest (31), or apoptosis, thereby, maintain genomic stability (32) and this may also reduce the therapeutic effectiveness (33). p53 wild-type cell lines, when irradiating with ATM were downregulated, p53 cannot be retarded and lead to cell cycle checkpoint deficiency (1).…”

Section: Discussionmentioning

confidence: 99%

miR-30a radiosensitizes non-small cell lung cancer by targeting ATF1 that is involved in the phosphorylation of ATM

et al. 2017

View full text Add to dashboard Cite

Increasing number of studies report that microRNAs play important roles in radiosensitization. miR-30a has been proved to perform many functions in the development and treatment of cancer, and it is downregulated in non-small cell lung cancer (NSCLC) tissues and cells. This study was conducted to understand if miR-30a plays a role in the radiosensitivity of NSCLC cells. Radiosensitivity was examed by colony survival assay and tumor volume changing in vitro and in vivo, respectively. Bioinformatic analysis and luciferase reporter assays were used to distinguish the candidate target of miR-30a. qRT-PCR and western blotting were carried out to detect the relative expression of mRNAs and proteins. Cell cycle and cell apoptosis were determined by flow cytometry. Our results illustrated miR-30a could increase the radiosensitivity of NSCLC, especially in A549 cell line. In vivo experiment also showed the potential radiosensitizing possibility of miR-30a. Further exploration validated that miR-30a was directly targeting activating transcription factor 1 (ATF1). In studying the ataxia-telangiectasia mutated (ATM) associated effects on cell radiosensitivity, we found that miR-30a could reduce radiation induced G2/M cell cycle arrest and may also affect radiation induced apoptosis. Together, our results demonstrated that miR-30a may modulate the radiosensitivity of NSCLC through reducing the function of ATF1 in phosphorylation of ATM and have potential therapeutic value.

show abstract

“…In other words, in the middle stages of PAH, the upregulated ATM seems to prevent PA-SMCs from growth in order to slow down the development of PAH. It is well established that ATM signaling arrests proliferation and induces apoptosis [ 25 – 27 ]. In our study, inhibition of ATM signaling seemed to enhance PA-SMCs proliferation.…”

Section: Discussionmentioning

confidence: 99%

Ataxia-Telangiectasia Mutated (ATM) Protein Signaling Participates in Development of Pulmonary Arterial Hypertension in Rats

Liu

et al. 2017

Med Sci Monit

View full text Add to dashboard Cite

BackgroundPrevious studies revealed physiological and pathogenetic similarity between vascular smooth muscles cells with severe pulmonary arterial hypertension and tumors. The DNA damage response was found in both pulmonary arterial hypertension (PAH) cells and tumors. The ataxia-telangiectasia mutated proteins (ATM) pathway is considered an important factor in the DNA damage response of tumor formation, but its function in the development of PAH remains unknown.Material/MethodsThe Sprague-Dawley rat PAH model was established. Three weeks (Group M1), 5 weeks (Group M2), and 7 weeks (Group M3) after drug injection, pulmonary expression of ATM, Checkpoint kinase 2 (Chk2), P53, and P21 were measured. A section of the lungs from Group M2 was used for pulmonary artery vascular smooth muscles cells (PA-SMCs) isolation and culture. The effect of KU60019 in the proliferation and apoptosis of primary cultured rat PA-SMCs was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and TdT-mediated dUTP nick-end labeling (TUNEL), respectively.ResultsImmunohistochemistry results show that the expression of ATM, Chk2, and P21 increased in Groups M1 and M2, and decreased in Group M3. Additionally, expression of P53 increased in Group M1, and decreased in Groups M2 and M3. RT-PCR and Western blotting demonstrated that in Groups M1 and M2, the expression of ATM, Chk2, P53, and P21 increased, whereas it decreased in Group M3. In cell culture, 0.3 μM and 0.5 μM KU60019 increased the growth of PA-SMCs, and 0.5 μM KU60019 reduced cell apoptosis.ConclusionsExpression of the ATM-Chk2 pathway increased in early stages of PAH formation, but decreased in late stages. In primary cultured PA-SMCs, KU60019 increased cell proliferation and inhibited cell apoptosis.

show abstract

Sodium glycididazole enhances the radiosensitivity of laryngeal cancer cells through downregulation of ATM signaling pathway

Cited by 10 publications

References 25 publications

Preclinical study on hypoxic radiosensitizing effects of glycididazole in comparison with those of doranidazole inï¿½vitro and inï¿½vivo

Preclinical study on hypoxic radiosensitizing effects of glycididazole in comparison with those of doranidazole inï¿½vitro and inï¿½vivo

miR-30a radiosensitizes non-small cell lung cancer by targeting ATF1 that is involved in the phosphorylation of ATM

Ataxia-Telangiectasia Mutated (ATM) Protein Signaling Participates in Development of Pulmonary Arterial Hypertension in Rats

Contact Info

Product

Resources

About