Lovastatin sensitizes lung cancer cells to ionizing radiation: Modulation of molecular pathways of radioresistance and tumor suppression

Journal of Thoracic Oncology

Volumn 6, Issue 3, 2011, Pages 439-450

  Sanli, Toran ^a,b   Liu, Caiqiong ^a   Rashid, Ayesha ^a,b   Hopmans, Sarah N ^c   Tsiani, Evangelia ^d   Schultz, Carrie ^a   Farrell, Thomas ^a,e   Singh, Gurmit ^c   Wright, James ^a,b   Tsakiridis, Theodoros ^a,b  

^a JURAVINSKI CANCER CENTRE   (Canada)

^b MCMASTER UNIVERSITY   (Canada)

^c Department of Pathology Molecular Medicine ^*  (Canada)

^d MCMASTER UNIVERSITY   (Canada)

^e BROCK UNIVERSITY   (Canada)

Author keywords

A549 cells; Akt; AMPK; Apoptosis; Cell cycle; Cleaved caspase 3; EGFR; Erk; Lovastatin; Lung cancer; Radiation sensitizer

Indexed keywords

CASPASE 3; CYCLIN DEPENDENT KINASE INHIBITOR 1; CYCLIN DEPENDENT KINASE INHIBITOR 1B; MEVINOLIN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PROTEIN KINASE B;

APOPTOSIS; ARTICLE; CANCER CELL; CANCER INHIBITION; CELL CYCLE; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL CYCLE S PHASE; CELL PROLIFERATION; CELL SURVIVAL; CLONOGENIC ASSAY; CONTROLLED STUDY; DRUG MECHANISM; HUMAN; HUMAN CELL; IONIZING RADIATION; LUNG ADENOCARCINOMA; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN PHOSPHORYLATION; RADIOSENSITIVITY; RADIOSENSITIZATION; SIGNAL TRANSDUCTION;

EID: 79951768538     PISSN: 15560864     EISSN: 15561380     Source Type: Journal    
DOI: 10.1097/JTO.0b013e3182049d8b     Document Type: Article

References (52)

1. Schuurbiers OC, Kaanders JH, van der Heijden HF, et al. The PI3-K/ AKT-pathway and radiation resistance mechanisms in non-small cell lung cancer. J Thorac Oncol 2009;4:761-767.
2. Bernhard EJ, Maity A, Muschel RJ, et al. Effects of ionizing radiation on cell cycle progression. A review. Radiat Environ Biophys 1995; 34:79-83.
3. Hartlerode AJ, Scully R. Mechanisms of double-strand break repair in somatic mammalian cells. Biochem J 2009;423:157-168.
4. Vidal A, Koff A. Cell-cycle inhibitors: three families united by a common cause. Gene 2000;247:1-15. (Pubitemid 30201556)
5. Sanli T, Rashid A, Liu C, et al. Ionizing radiation activates AMPactivated kinase (AMPK): a target for radiosensitization of human cancer cells. Int J Radiat Oncol Biol Phys 2010;78:221-229.
6. Park CM, Park MJ, Kwak HJ, et al. Ionizing radiation enhances matrix metalloproteinase-2 secretion and invasion of glioma cells through Src/epidermal growth factor receptor-mediated p38/Akt and phosphatidylinositol 3-kinase/Akt signaling pathways. Cancer Res 2006;66:8511-8519.
7. Zimmermann M, Zouhair A, Azria D, et al. The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications. Radiat Oncol 2006;1:11.
8. Nakamura JL, Karlsson A, Arvold ND, et al. PKB/Akt mediates radiosensitization by the signaling inhibitor LY294002 in human malignant gliomas. J Neurooncol 2005;71:215-222. (Pubitemid 40372948)
9. Le Tourneau C, Siu LL. Molecular-targeted therapies in the treatment of squamous cell carcinomas of the head and neck. Curr Opin Oncol 2008;20:256-263. (Pubitemid 351507544)
10. Fritz G, Kaina B. Rho GTPases: promising cellular targets for novel anticancer drugs. Curr Cancer Drug Targets 2006;6:1-14.
11. Bernhard EJ, Stanbridge EJ, Gupta S, et al. Direct evidence for the contribution of activated N-ras and K-ras oncogenes to increased intrinsic radiation resistance in human tumor cell lines. Cancer Res 2000;60: 6597-6600.
12. Lerner EC, Zhang TT, Knowles DB, et al. Inhibition of the prenylation of K-Ras, but not H- or N-Ras, is highly resistant to CAAX peptidomimetics and requires both a farnesyltransferase and a geranylgeranyltransferase I inhibitor in human tumor cell lines. Oncogene 1997;15:1283-1288. (Pubitemid 27429743)
13. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature 1990;343:425-430.
14. Chan KK, Oza AM, Siu LL. The statins as anticancer agents. Clin Cancer Res 2003;9:10-19. (Pubitemid 36109711)
15. Sassano A, Platanias LC. Statins in tumor suppression. Cancer Lett 2008;260:11-19.
16. Poynter JN, Gruber SB, Higgins PD, et al. Statins and the risk of colorectal cancer. N Engl J Med 2005;352:2184-2192. (Pubitemid 40727085)
17. Khurana V, Bejjanki HR, Caldito G, et al. Statins reduce the risk of lung cancer in humans: a large case-control study of US veterans. Chest 2007;131:1282-1288. (Pubitemid 46762329)
18. Platz EA, Leitzmann MF, Visvanathan K, et al. Statin drugs and risk of advanced prostate cancer. J Natl Cancer Inst 2006;98:1819-1825. (Pubitemid 46017933)
19. Hamilton RJ, Banez LL, Aronson WJ, et al. Statin medication use and the risk of biochemical recurrence after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. Cancer 2010;116:3389-3398.
20. Kollmeier MA, Katz MS, Mak K, et al. Improved biochemical outcomes with statin use in patients with high-risk localized prostate cancer treated with radiotherapy. Int J Radiat Oncol Biol Phys In press.
21. 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;28:2653-2659.
22. Maksimova E, Yie TA, Rom WN. In vitro mechanisms of lovastatin on lung cancer cell lines as a potential chemopreventive agent. Lung 2008;186:45-54.
23. Tsakiridis T, Vranic M, Klip A. Disassembly of the actin network inhibits insulin-dependent stimulation of glucose transport and prevents recruitment of glucose transporters to the plasma membrane. J Biol Chem 1994;269:29934-29942. (Pubitemid 24365162)
24. Liu SK, Coackley C, Krause M, et al. A novel poly(ADP-ribose) polymerase inhibitor, ABT-888, radiosensitizes malignant human cell lines under hypoxia. Radiother Oncol 2008;88:258-268.
25. Motoshima H, Goldstein BJ, Igata M, et al. AMPK and cell proliferation- AMPK as a therapeutic target for atherosclerosis and cancer. J Physiol 2006;574:63-71. (Pubitemid 43905797)
26. Janicke RU, Sprengart ML, Wati MR, et al. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 1998;273:9357-9360. (Pubitemid 28183012)
27. Fritz G, Brachetti C, Kaina B. Lovastatin causes sensitization of HeLa cells to ionizing radiation-induced apoptosis by the abrogation of G2 blockage. Int J Radiat Biol 2003;79:601-610. (Pubitemid 37297218)
28. Khanzada UK, Pardo OE, Meier C, et al. Potent inhibition of small-cell lung cancer cell growth by simvastatin reveals selective functions of Ras isoforms in growth factor signalling. Oncogene 2006;25:877-887. (Pubitemid 43237706)
29. Bellini MJ, Polo MP, de Alaniz MJ, et al. Effect of simvastatin on the uptake and metabolic conversion of palmitic, dihomo-gamma-linoleic and alpha-linolenic acids in A549 cells. Prostaglandins Leukot Essent Fatty Acids 2003;69:351-357. (Pubitemid 37346669)
30. Valenzuela DM, Groffen J. Four human carcinoma cell lines with novel mutations in position 12 of c-K-ras oncogene. Nucleic Acids Res 1986; 14:843-852. (Pubitemid 16136140)
31. Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 2006;441:424-430. (Pubitemid 44050136)
32. Gupta S, Ramjaun AR, Haiko P, et al. Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice. Cell 2007;129:957-968. (Pubitemid 46802703)
33. Mantha AJ, Hanson JE, Goss G, et al. Targeting the mevalonate pathway inhibits the function of the epidermal growth factor receptor. Clin Cancer Res 2005;11:2398-2407. (Pubitemid 40490201)
34. Mistafa O, Stenius U. Statins inhibit Akt/PKB signaling via P2X7 receptor in pancreatic cancer cells. Biochem Pharmacol 2009;78:1115-1126.
35. 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;76:143-150. (Pubitemid 41725440)
36. Toulany M, Kasten-Pisula U, Brammer I, et al. Blockage of epidermal growth factor receptor-phosphatidylinositol 3-kinase-AKT signaling increases radiosensitivity of K-RAS mutated human tumor cells in vitro by affecting DNA repair. Clin Cancer Res 2006;12:4119-4126. (Pubitemid 44078101)
37. Gupta AK, McKenna WG, Weber CN, et al. Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction. Clin Cancer Res 2002;8:885-892. (Pubitemid 34742122)
38. Sanchez-Cespedes M, Parrella P, Esteller M, et al. Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. Cancer Res 2002;62:3659-3662. (Pubitemid 34728843)
39. Steinberg GR, Kemp BE. AMPK in health and disease. Physiol Rev 2009;89:1025-1078.
40. Sun W, Lee TS, Zhu M, et al. Statins activate AMP-activated protein kinase in vitro and in vivo. Circulation 2006;114:2655-2662. (Pubitemid 44967349)
41. Kim KY, Baek A, Hwang JE, et al. Adiponectin-activated AMPK stimulates dephosphorylation of AKT through protein phosphatase 2A activation. Cancer Res 2009;69:4018-4026.
42. Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer 2009;9:563-575.
43. Niculescu AB III, Chen X, Smeets M, et al. Effects of p21(Cip1/Waf1) at both the G1/S and the G2/M cell cycle transitions: pRb is a critical determinant in blocking DNA replication and in preventing endoreduplication. Mol Cell Biol 1998;18:629-643. (Pubitemid 28021073)
44. Woodard J, Sassano A, Hay N, et al. Statin-dependent suppression of the Akt/mammalian target of rapamycin signaling cascade and programmed cell death 4 up-regulation in renal cell carcinoma. Clin Cancer Res 2008;14:4640-4649.
45. Boehme KA, Kulikov R, Blattner C. p53 stabilization in response to DNA damage requires Akt/PKB and DNA-PK. Proc Natl Acad Sci USA 2008;105:7785-7790. (Pubitemid 351872716)
46. Laezza C, Fiorentino L, Pisanti S, et al. Lovastatin induces apoptosis of k-ras-transformed thyroid cells via inhibition of ras farnesylation and by modulating redox state. J Mol Med 2008;86:1341-1351.
47. Keyomarsi K, Sandoval L, Band V, et al. Synchronization of tumor and normal cells from G1 to multiple cell cycles by lovastatin. Cancer Res 1991;51:3602-3609.
48. Bouterfa HL, Sattelmeyer V, Czub S, et al. Inhibition of Ras farnesylation by lovastatin leads to downregulation of proliferation and migration in primary cultured human glioblastoma cells. Anticancer Res 2000;20:2761-2771. (Pubitemid 30614496)
49. Dimitroulakos J, Ye LY, Benzaquen M, et al. Differential sensitivity of various pediatric cancers and squamous cell carcinomas to lovastatininduced apoptosis: therapeutic implications. Clin Cancer Res 2001;7: 158-167. (Pubitemid 32110219)
50. Wu J, Wong WW, Khosravi F, et al. Blocking the Raf/MEK/ERK pathway sensitizes acute myelogenous leukemia cells to lovastatininduced apoptosis. Cancer Res 2004;64:6461-6468. (Pubitemid 39297901)
51. Sleijfer S, van der Gaast A, Planting AS, et al. The potential of statins as part of anti-cancer treatment. Eur J Cancer 2005;41:516-522. (Pubitemid 40292731)
52. Knox JJ, Siu LL, Chen E, et al. A phase I trial of prolonged administration of lovastatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or of the cervix. Eur J Cancer 2005;41:523-530. (Pubitemid 40292732)