Radiosensitization effect of zidovudine on human malignant glioma cells
Section snippets
Materials and methods
Experimental groupings. Human malignant glioma cells U251 (CCTCC) were cultured in RPMI 1640 media supplement with 10% calf serum (Gibco). Cells were incubated at 37 °C in humidified atmosphere containing 5% CO2. Exponentially growing cells in 50 cm2 culture flasks were divided into four groups: (1) Control: without AZT or irradiation treatment; (2) Irradiation: treated with irradiation (60Co therapeutic machine, GWXJ80 type, Chengdu, China. Radiation dose: 2Gy at the rate of 61.22 cGy/min, SSD = 80
Increase of TA by irradiation and decrease of TA by AZT
A significant increase in TA was observed between irradiation group and control group (1.902 ± 0.224 vs. 1.567 ± 0.037, p < 0.05). We can see gradual up-regulation of TA in irradiation group after 2Gy-radiation exposure, and nearly maximum at 6 h (increased by about 40%). Obviously, TA decreased in drug group compared to control group (1.019 ± 0.116 vs. 1.567 ± 0.037, p < 0.05). It indicated that AZT could suppress the TA of the U251 cells. Compared to the irradiation group, the TA in the drug and
Discussion
In this report, we have observed that, after in vitro exposure to 2Gy γ-radiation, telomerase activation has been increased in U251 cells and reached a maximum at 6 h postirradiation, confirming that low dose irradiation can induce an up-regulation of TA in tumor cell lines [4], [5]. We favor the hypothesis that telomerase may participate in the process of DNA repair and the up-regulation of TA may be a reaction to DNA damage induced by irradiation, which may be one of the mechanisms involved in
Acknowledgments
We are grateful to Dr Wen Jie Zhang for critical review of the manuscript. This work was supported by the Natural Science Foundation of China (30171063).
References (34)
- et al.
The structure of telomeric DNA
Curr. Opin. Struct. Biol.
(2003) - et al.
DNA end-joining: from yeast to man
Trends Biochem. Sci.
(1998) Involvement of telomeric sequences in chromosomal aberration
Mutat. Res.
(1998)- et al.
Reversible manipulation of telomerase expression and telomere length. Implications for the ionizing radiation response and replicative senescence of human cells
J. Biol. Chem.
(2002) - et al.
Accumulation of single-strand breaks is the major cause of telomere shortening in human fibroblasts
Radical Biol. Med.
(2000) - et al.
Preferential accumulation of single-stranded regions in telomeres of human fibroblasts
Exp. Cell Res.
(1998) - et al.
Radiation-induced DNA double-strand breaks and the radiosensitivity of human cells: a closer look
Biochime
(1997) - et al.
Induction of telomerase activity by in vivo X-irradiation of mouse splenocytes and its possible role in chromosome healing
Mutat. Res.
(1998) - et al.
Shortened telomeres join to DNA breaks interfering with their correct repair
Exp. Cell Res.
(2003) Telomeres and cancer: a tale with many endings
Curr. Opin. Genet. Dev.
(2003)
The telomere protein Taz1 is required to prevent and repair genomic DNA breaks
Mol. Cell
Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast
Cell
Specific association of human telomerase activity with immortal cells and cancer
Science
Replicative senescence and cell immortality: the role of telomeres and telomerase
Proc. Soc. Exp. Bio. Med.
Telomerase as an anti-cancer target: current status and future prospects
Anticancer Drug. Des.
Induction of telomerase activity by irradiation in human lymphoblasts
Radiat. Res.
Radiation-induced changes of telomerase activity in a human Ewing xenograft tumor
Strahlenther. Onkol.
Cited by (40)
Targeting telomerase and telomeres to enhance ionizing radiation effects in in vitro and in vivo cancer models
2017, Mutation Research - Reviews in Mutation ResearchCitation Excerpt :In 2007, Zhou and coworkers demonstrated radiosensitizing properties of AZT in U251 glioma cells. Authors reported that the combined AZT and X-rays treatment delayed DNA repair kinetics of SSB and DSB in the first 6 h after irradiation and decreased the surviving fraction (D0 value of 1.8 and 1.4 Gy in X-ray treated cells and AZT + X-ray treated cells, respectively) [119]. These data were in line with those reported by Hiraoka and collegues in the Chinese hamster V79 cell line [120].
Glycosmis pentaphylla (Retz.) DC arrests cell cycle and induces apoptosis via caspase-3/7 activation in breast cancer cells
2015, Journal of EthnopharmacologyMolecular geometry, vibrational spectra, atomic charges, frontier molecular orbital and Fukui function analysis of antiviral drug zidovudine
2012, Spectrochimica Acta - Part A: Molecular and Biomolecular SpectroscopyCitation Excerpt :Unfortunately, viral mutations leading to drug resistance and harmful side effects of the current medicines have identified the need for new drugs to combat HIV. Zidovudine, 3-azido-3-deoxythymidine (AZT), is an organic compound used to delay the development of Acquired Immune Deficiency Syndrome (AIDS) in patients infected with HIV, to reduce mother-to child HIV transmission and as radio sensitizer in cancer radiotherapy, because it is a telomerase inhibitor with potential anticancer properties [1]. Jerome Horowitz first synthesized AZT in the year 1964 [2].
Polyphenolic fraction of Pilea microphylla (L.) protects Chinese hamster lung fibroblasts against γ-radiation-induced cytotoxicity and genotoxicity
2012, Environmental Toxicology and PharmacologyXPC is essential for nucleotide excision repair of zidovudine-induced DNA damage in human hepatoma cells
2011, Toxicology and Applied PharmacologyCitation Excerpt :When AZT becomes incorporated into host DNA chains, it lacks the necessary ribose moiety required for DNA chain extension and therefore acts as a DNA chain terminator. The genotoxic manifestations of this incorporation, including micronuclei (Von Tungeln et al., 2004, 2007; Borojerdi et al., 2009), sister chromatic exchange, chromosomal aberrations (Olivero et al., 1994; Wutzler and Thust, 2001), and telomere shortening (Zhou et al., 2007), have been well documented (IARC, 2000). AZT treatment has been shown to induce apoptosis in mice skeletal muscle cells (Desai et al., 2009), mice myocardium (Purevjav et al., 2007), human adipocytes (McComsey et al., 2005), human liver HepG2 and THLE2 cells (Fang and Beland, 2009), and human parathyroid cancer cells (Falchetti et al., 2005).
- 1
These authors contributed equally to this work.