Potential use of HMG-CoA reductase inhibitors (statins) as radioprotective agents

British Medical Bulletin

Volumn 97, Issue 1, 2011, Pages 17-26

  Fritz, Gerhard ^a   Henninger, Christian ^a   Huelsenbeck, Johannes ^a  

^a JOHANNES GUTENBERG UNIVERSITY   (Germany)

Author keywords

DNA damage response; DNA repair; HMG CoA reductase inhibitors; ionizing radiation; normal tissue damage; Rho GTPases

Indexed keywords

BETA ACTIN; CELL NUCLEUS DNA; CONNECTIVE TISSUE GROWTH FACTOR; DOUBLE STRANDED DNA; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; GAMMA TOCOTRIENOL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; MESSENGER RNA; MEVINOLIN; PHOSPHATIDYLINOSITOL 3 KINASE; PRAVASTATIN; PROTEIN KINASE B; RADIOPROTECTIVE AGENT; RAS PROTEIN; SIMVASTATIN; TUMOR NECROSIS FACTOR ALPHA;

ARTICLE; ATHEROSCLEROSIS; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL DEATH; CYTOKINE PRODUCTION; DNA DAMAGE; DNA REPAIR; DOUBLE STRANDED DNA BREAK; DOWN REGULATION; DRUG MECHANISM; FIBROSIS; GENOMIC INSTABILITY; INFLAMMATION; IONIZING RADIATION; NONHUMAN; PERITONITIS; PRIORITY JOURNAL; RADIATION INJURY; RADIATION PROTECTION; RADIOSENSITIVITY; TISSUE INJURY;

DNA DAMAGE; DNA REPAIR; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; RADIATION INJURIES; RADIATION-PROTECTIVE AGENTS; RADIOTHERAPY;

EID: 79952562134     PISSN: 00071420     EISSN: 14718391     Source Type: Journal    
DOI: 10.1093/bmb/ldq044     Document Type: Article

References (40)

1. Ellenbroek SI, Collard JG. Rho GTPases: functions and association with cancer. Clin Exp Metastasis 2007;24:657-72. (Pubitemid 50002983)
2. Hall A. The cytoskeleton and cancer. Cancer Metastasis Rev 2009;28:5-14.
3. Ludman A, Venugopal V, Yellon DM et al. Statins and cardioprotection-more than just lipid lowering? Pharmacol Ther 2009;122:30-43.
4. Zhou Q, Liao JK. Pleiotropic effects of statins-basic research and clinical perspectives. Circ J 2010;74:818-26.
5. Fritz G. Targeting the mevalonate pathway for improved anticancer therapy. Curr Cancer Drug Targets 2009;9:626-38.
6. Wang CY, Liu PY, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med 2008;14:37-44.
7. Harper JW, Elledge SJ. The DNA damage response: ten years after. Mol Cell 2007;28:739-45. (Pubitemid 350217064)
8. Jeggo P, Lobrich M. Radiation-induced DNA damage responses. Radiat Prot Dosim 2006;122:124-7. (Pubitemid 47090437)
9. Jeggo PA, Lobrich M. Contribution of DNA repair and cell cycle checkpoint arrest to the maintenance of genomic stability. DNA Repair (Amst) 2006;5:1192-98. (Pubitemid 44308466)
10. O'Driscoll M, Jeggo PA. The role of double-strand break repair-insights from human genetics. Nat Rev Genet 2006;7:45-54. (Pubitemid 41828947)
11. Roos WP, Kaina B. DNA damage-induced cell death by apoptosis. Trends Mol Med 2006;12:440-50. (Pubitemid 44291571)
12. Dent P, Yacoub A, Contessa J et al. Stress and radiation-induced activation of multiple intracellular signaling pathways. Radiat Res 2003;159:283-300. (Pubitemid 36314943)
13. Tamaishi N, Tsukimoto M, Kitami A et al. P2Y6 receptors and ADAM17 mediate low-dose gamma-ray-induced focus formation (activation) of EGF receptor. Radiat Res 2010: Dec 3 Epub ahead of print.
14. Hallahan D, Kuchibhotla J, Wyble C. Cell adhesion molecules mediate radiation-induced leukocyte adhesion to the vascular endothelium. Cancer Res 1996;56:5150-5. (Pubitemid 26383029)
15. Adams MJ, Lipshultz SE, Schwartz C et al. Radiation-associated cardiovascular disease: manifestations and management. Semin Radiat Oncol 2003;13:346-56. (Pubitemid 36962655)
16. Sprung CN, Vasireddy RS, Karagiannis TC et al. Methylproamine protects against ionizing radiation by preventing DNA double-strand breaks. Mutat Res 2010;692:49-52.
17. Sinn B, Schulze J, Schroeder G et al. Pifithrin-alpha as a potential cytoprotective agent in radiotherapy: protection of normal tissue without decreasing therapeutic efficacy in glioma cells. Radiat Res 2010;174:601-10.
18. Southgate TD, Sheard V, Milsom MD et al. Radioprotective gene therapy through retroviral expression of manganese superoxide dismutase. J Gene Med 2006;8:557-65. (Pubitemid 43827249)
19. Quist-Paulsen P. Statins and inflammation: an update. Curr Opin Cardiol 2010;25:399-405.
20. Zhao H, Liao Y, Minamino T et al. Inhibition of cardiac remodeling by pravastatin is associated with amelioration of endoplasmic reticulum stress. Hypertens Res 2008;31:1977-87.
21. Fitzgerald JP, Chou SY, Franco I et al. Atorvastatin ameliorates tubulointerstitial fibrosis and protects renal function in chronic partial ureteral obstruction cases. J Urol 2009;182:1860-8.
22. Nuebel T, Damrot J, Roos WP et al. Lovastatin protects human endothelial cells from killing by ionizing radiation without impairing induction and repair of DNA double-strand breaks. Clin Cancer Res 2006;12:933-9. (Pubitemid 43259876)
23. Ostrau C, Hulsenbeck J, Herzog M et al. Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo. Radiother Oncol 2009;92:492-9.
24. Haydont V, Mathe D, Bourgier C et al. Induction of CTGF by TGF-beta1 in normal and radiation enteritis human smooth muscle cells: Smad/Rho balance and therapeutic perspectives. Radiother Oncol 2005;76:219-25. (Pubitemid 41725451)
25. Wang J, Boerma M, Fu Q et al. Simvastatin ameliorates radiation enteropathy development after localized, fractionated irradiation by a protein C-independent mechanism. Int J Radiat Oncol Biol Phys 2007;68:1483-90. (Pubitemid 47176821)
26. Haydont V, Bourgier C, Pocard M et al. Pravastatin inhibits the Rho/CCN2/extracellular matrix cascade in human fibrosis explants and improves radiation-induced intestinal fibrosis in rats. Clin Cancer Res 2007;13:5331-40. (Pubitemid 47510357)
27. Holler V, Buard V, Gaugler MH et al. Pravastatin limits radiation-induced vascular dysfunction in the skin. J Invest Dermatol 2009;129:1280-91.
28. Kim JW, Rhee CK, Kim TJ et al. Effect of pravastatin on bleomycin-induced acute lung injury and pulmonary fibrosis. Clin Exp Pharmacol Physiol 2010;37:1055-63.
29. Toulany M, Dittmann K, Kruger M et al. Radioresistance of K-Ras mutated human tumor cells is mediated through EGFR-dependent activation of PI3K-AKT pathway. Radiother Oncol 2005;76:143-50. (Pubitemid 41725440)
30. Cengel KA, Deutsch E, Stephens TC et al. Radiosensitizing effects of the prenyltransferase inhibitor AZD3409 against RAS mutated cell lines. Cancer Biol Ther 2006;5:1206-10. (Pubitemid 44772239)
31. Miller AC, Kariko K, Myers CE et al. Increased radioresistance of EJras-transformed human osteosarcoma cells and its modulation by lovastatin, an inhibitor of p21ras isoprenylation. Int J Cancer 1993;53:302-7. (Pubitemid 23042883)
32. Gutt R, Tonlaar N, Kunnavakkam R et al. Statin use and risk of prostate cancer recurrence in men treated with radiation therapy. J Clin Oncol 2010;28:2653-9.
33. Bourgier C, Haydont V, Milliat F et al. Inhibition of Rho kinase modulates radiation induced fibrogenic phenotype in intestinal smooth muscle cells through alteration of the cytoskeleton and connective tissue growth factor expression. Gut 2005;54:336-43. (Pubitemid 40299087)
34. Monceau V, Pasinetti N, Schupp C et al. Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity. Curr Drug Targets 2010;11:1395-404.
35. Rodemann HP, Dittmann K, Toulany M. Radiation-induced EGFR-signaling and control of DNA-damage repair. Int J Radiat Biol 2007;83:781-91. (Pubitemid 350219102)
36. Kriegs M, Kasten-Pisula U, Rieckmann T et al. The epidermal growth factor receptor modulates DNA double-strand break repair by regulating non-homologous end-joining. DNA Repair (Amst) 2010;9:889-97.
37. Mahmoudi M, Gorenne I, Mercer J et al. Statins use a novel Nijmegen breakage syndrome-1- dependent pathway to accelerate DNA repair in vascular smooth muscle cells. Circ Res 2008;103:717-25.
38. Pernice F, Floccari F, Caccamo C et al. Chromosomal damage and atherosclerosis. A protective effect from simvastatin. Eur J Pharmacol 2006;532:223-9.
39. Sandrock K, Bielek H, Schradi K et al. The nuclear import of the small GTPase Rac1 is mediated by the direct interaction with karyopherin alpha2. Traffic 2010;11:198-209.
40. Guerra L, Carr HS, Richter-Dahlfors A et al. A bacterial cytotoxin identifies the RhoA exchange factor Net1 as a key effector in the response to DNA damage. PLoS One 2008;3:e2254.