Late ROS Accumulation and Radiosensitivity in SOD1-overexpressing Human Glioma Cells

Overview

Journal Free Radic Biol Med

Specialties Biochemistry
Biology
General Medicine

Date 2008 Sep 16

PMID 18790046

Citations 38

Authors

Zhen Gao

Ehab H Sarsour

Amanda L Kalen

Ling Li

Maneesh G Kumar

Prabhat C Goswami

Affiliations

Soon will be listed here.

Abstract

This study investigates the hypothesis that CuZn superoxide dismutase (SOD1) overexpression confers radioresistance to human glioma cells by regulating the late accumulation of reactive oxygen species (ROS) and the G(2)/M-checkpoint pathway. U118-9 human glioma cells (wild type, neo vector control, and stably overexpressing SOD1) were irradiated (0-10 Gy) and assayed for cell survival, cellular ROS levels, cell-cycle-phase distributions, and cyclin B1 expression. SOD1-overexpressing cells were radioresistant compared to wild-type (wt) and neo vector control (neo) cells. Irradiated wt and neo cells showed a significant increase (approximately twofold) in DHE fluorescence beginning at 2 days postirradiation, which remained elevated at 8 days postirradiation. Interestingly, the late accumulation of ROS was suppressed in irradiated SOD1-overexpressing cells. The increase in ROS levels was followed by a decrease in cell growth and viability and an increase in the percentage of cells with sub-G(1) DNA content. SOD1 overexpression enhanced radiation-induced G(2) accumulation within 24 h postirradiation, which was accompanied by a decrease in cyclin B1 mRNA and protein levels. These results support the hypothesis that long after radiation exposure a "metabolic redox response" regulates radiosensitivity of human glioma cells.

Citing Articles

Gene therapy for atrial fibrillation.

Mo W, Donahue J J Mol Cell Cardiol. 2024; 196:84-93.

PMID: 39270930 PMC: 11534567. DOI: 10.1016/j.yjmcc.2024.09.004.

Superoxide dismutase 1 mediates adaptation to the tumor microenvironment of glioma cells via mammalian target of rapamycin complex 1.

Konig S, Strassheimer F, Brandner N, Schroder J, Urban H, Harwart L Cell Death Discov. 2024; 10(1):379.

PMID: 39187509 PMC: 11347576. DOI: 10.1038/s41420-024-02145-6.

Radioprotective effect of the anti-diabetic drug metformin.

Siteni S, Barron S, Luitel K, Shay J PLoS One. 2024; 19(7):e0307598.

PMID: 39042641 PMC: 11265658. DOI: 10.1371/journal.pone.0307598.

Pharmacological ascorbate induces sustained mitochondrial dysfunction.

Carroll R, Du J, OLeary B, Steers G, Goswami P, Buettner G Free Radic Biol Med. 2023; 204:108-117.

PMID: 37137343 PMC: 10375417. DOI: 10.1016/j.freeradbiomed.2023.04.023.

Effects of Antioxidant Gene Overexpression on Stress Resistance and Malignization In Vitro and In Vivo: A Review.

Tavleeva M, Belykh E, Rybak A, Rasova E, Chernykh A, Ismailov Z Antioxidants (Basel). 2022; 11(12).

PMID: 36552527 PMC: 9774954. DOI: 10.3390/antiox11122316.

References

Menon S, Goswami P . A redox cycle within the cell cycle: ring in the old with the new. Oncogene. 2006; 26(8):1101-9. DOI: 10.1038/sj.onc.1209895. View

Oberley L, Lindgren L, Baker S, Stevens R . Superoxide lon as the cause of the oxygen effect. Radiat Res. 1976; 68(2):320-8. View

Tarpey M, Fridovich I . Methods of detection of vascular reactive species: nitric oxide, superoxide, hydrogen peroxide, and peroxynitrite. Circ Res. 2001; 89(3):224-36. DOI: 10.1161/hh1501.094365. View

Castro M, Cowen R, Williamson I, David A, Jimenez-Dalmaroni M, Yuan X . Current and future strategies for the treatment of malignant brain tumors. Pharmacol Ther. 2003; 98(1):71-108. DOI: 10.1016/s0163-7258(03)00014-7. View

Guo G, Yan-Sanders Y, Lyn-Cook B, Wang T, Tamae D, Ogi J . Manganese superoxide dismutase-mediated gene expression in radiation-induced adaptive responses. Mol Cell Biol. 2003; 23(7):2362-78. PMC: 150726. DOI: 10.1128/MCB.23.7.2362-2378.2003. View

Kurisaka M, Mori K . Immunohistochemical study of medulloblastoma with a monoclonal antibody against human copper and zinc-superoxide dismutase. Neurol Med Chir (Tokyo). 1996; 36(4):220-3. DOI: 10.2176/nmc.36.220. View

Petkau A, Chelack W, Pleskach S . Letter: Protection of post-irradiated mice by superoxide dismutase. Int J Radiat Biol Relat Stud Phys Chem Med. 1976; 29(3):297-9. DOI: 10.1080/09553007614550341. View

Zhang Y, Zhao W, Zhang H, Domann F, Oberley L . Overexpression of copper zinc superoxide dismutase suppresses human glioma cell growth. Cancer Res. 2002; 62(4):1205-12. View

Scaife R . G2 cell cycle arrest, down-regulation of cyclin B, and induction of mitotic catastrophe by the flavoprotein inhibitor diphenyleneiodonium. Mol Cancer Ther. 2004; 3(10):1229-37. View

10.

Summers R, Maves B, Reeves R, Arjes L, Oberley L . Irradiation increases superoxide dismutase in rat intestinal smooth muscle. Free Radic Biol Med. 1989; 6(3):261-70. DOI: 10.1016/0891-5849(89)90053-1. View

11.

Kang S, Rabbani Z, Folz R, Golson M, Huang H, Yu D . Overexpression of extracellular superoxide dismutase protects mice from radiation-induced lung injury. Int J Radiat Oncol Biol Phys. 2003; 57(4):1056-66. DOI: 10.1016/s0360-3016(03)01369-5. View

12.

McCord J, Fridovich I . Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969; 244(22):6049-55. View

13.

Weydert C, Smith B, Xu L, Kregel K, Ritchie J, Davis C . Inhibition of oral cancer cell growth by adenovirusMnSOD plus BCNU treatment. Free Radic Biol Med. 2003; 34(3):316-29. DOI: 10.1016/s0891-5849(02)01245-5. View

14.

St Clair D, Wan X, Oberley T, Muse K, St Clair W . Suppression of radiation-induced neoplastic transformation by overexpression of mitochondrial superoxide dismutase. Mol Carcinog. 1992; 6(4):238-42. DOI: 10.1002/mc.2940060404. View

15.

Ward J . DNA damage as the cause of ionizing radiation-induced gene activation. Radiat Res. 1994; 138(1 Suppl):S85-8. View

16.

Folz R, Crapo J . Extracellular superoxide dismutase (SOD3): tissue-specific expression, genomic characterization, and computer-assisted sequence analysis of the human EC SOD gene. Genomics. 1994; 22(1):162-71. DOI: 10.1006/geno.1994.1357. View

17.

Valko M, Rhodes C, Moncol J, Izakovic M, Mazur M . Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006; 160(1):1-40. DOI: 10.1016/j.cbi.2005.12.009. View

18.

Biaglow J, Mitchell J, Held K . The importance of peroxide and superoxide in the X-ray response. Int J Radiat Oncol Biol Phys. 1992; 22(4):665-9. DOI: 10.1016/0360-3016(92)90499-8. View

19.

Spitz D, Azzam E, Li J, Gius D . Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: a unifying concept in stress response biology. Cancer Metastasis Rev. 2004; 23(3-4):311-22. DOI: 10.1023/B:CANC.0000031769.14728.bc. View

20.

Zhao H, Kalivendi S, Zhang H, Joseph J, Nithipatikom K, Vasquez-Vivar J . Superoxide reacts with hydroethidine but forms a fluorescent product that is distinctly different from ethidium: potential implications in intracellular fluorescence detection of superoxide. Free Radic Biol Med. 2003; 34(11):1359-68. DOI: 10.1016/s0891-5849(03)00142-4. View