Simvastatin inhibits cell growth and induces apoptosis and G0/G1 cell cycle arrest in hepatic cancer cells

International Journal of Molecular Medicine

Volumn 26, Issue 5, 2010, Pages 735-741

  Relja, Borna ^a   Meder, Frank ^a   Wilhelm, Kerstin ^a   Henrich, Dirk ^a   Marzi, Ingo ^a   Lehnert, Mark ^a  

^a UNIVERSITY HOSPITAL FRANKFURT   (Germany)

Author keywords

Apoptosis; Cancer; Cell cycle; Liver; Simvastatin

Indexed keywords

CYCLIN D1; CYCLIN DEPENDENT KINASE 1; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE 4; CYCLIN E; PROTEIN P19; PROTEIN P27; SIMVASTATIN;

APOPTOSIS; ARTICLE; CELL CYCLE ARREST; CELL CYCLE G0 PHASE; CELL CYCLE G1 PHASE; CELL STRAIN HEPG2; CONTROLLED STUDY; GENE EXPRESSION; HUMAN; HUMAN CELL; LIVER CELL CARCINOMA; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL CYCLE PROTEINS; G0 PHASE; G1 PHASE; HUMANS; LIVER NEOPLASMS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; SIMVASTATIN;

EID: 77957885426     PISSN: 11073756     EISSN: 1791244X     Source Type: Journal    
DOI: 10.3892/ijmm_00000520     Document Type: Article

References (42)

1. Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin 59: 225-249, 2009.
2. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M and Boyle P: Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 18: 581-592, 2007.
3. Kamangar F, Dores GM and Anderson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24: 2137-2150, 2006. (Pubitemid 46655601)
4. Roayaie S, Schwartz JD, Sung MW, et al: Recurrence of hepatocellular carcinoma after liver transplant: patterns and prognosis. Liver Transpl 10: 534-540, 2004.
5. Morris-Stiff G, Gomez D, de Liguori CN and Prasad KR: Surgical management of hepatocellular carcinoma: is the jury still out? Surg Oncol 18: 298-321, 2009.
6. Llovet JM, Burroughs A and Bruix J: Hepatocellular carcinoma. Lancet 362: 1907-1917, 2003.
7. El-Serag HB, Mason AC and Key C: Trends in survival of patients with hepatocellular carcinoma between 1977 and 1996 in the United States. Hepatology 33: 62-65, 2001.
8. Yuen MF, Cheng CC, Lauder IJ, Lam SK, Ooi CG and Lai CL: Early detection of hepatocellular carcinoma increases the chance of treatment: Hong Kong experience. Hepatology 31: 330-335, 2000.
9. Lee HS, Kim KM, Yoon JH, et al: Therapeutic efficacy of transcatheter arterial chemoembolization as compared with hepatic resection in hepatocellular carcinoma patients with compensated liver function in a hepatitis B virus-endemic area: a prospective cohort study. J Clin Oncol 20: 4459-4465, 2002.
10. Asnacios A, Fartoux L, Romano O, et al: Gemcitabine plus oxaliplatin (GEMOX) combined with cetuximab in patients with progressive advanced stage hepatocellular carcinoma: results of a multicenter phase 2 study. Cancer 112: 2733-2739, 2008. (Pubitemid 351969218)
11. Chou YY, Cheng AL and Hsu HC: Expression of P-glycoprotein and p53 in advanced hepatocellular carcinoma treated by single agent chemotherapy: clinical correlation. J Gastroenterol Hepatol 12: 569-575, 1997.
12. Goldstein JL and Brown MS: Regulation of the mevalonate pathway. Nature 343: 425-430, 1990.
13. Newman A, Clutterbuck RD, Powles RL and Millar JL: Selective inhibition of primary acute myeloid leukaemia cell growth by simvastatin. Leukemia 8: 2023-2029, 1994. (Pubitemid 24985714)
14. Ghosh-Choudhury N, Mandal CC, Ghosh-Choudhury N and Ghosh-Choudhury G: Simvastatin induces derepression of PTEN expression via NFkappaB to inhibit breast cancer cell growth. Cell Signal 22: 749-758, 2010.
15. Cho SJ, Kim JS, Kim JM, Lee JY, Jung HC and Song IS: Simvastatin induces apoptosis in human colon cancer cells and in tumor xenografts, and attenuates colitis-associated colon cancer in mice. Int J Cancer 123: 951-957, 2008.
16. Sekine Y, Furuya Y, Nishii M, Koike H, Matsui H and Suzuki K: Simvastatin inhibits the proliferation of human prostate cancer PC-3 cells via down-regulation of the insulin-like growth factor 1 receptor. Biochem Biophys Res Commun 372: 356-361, 2008.
17. Sanchez CA, Rodriguez E, Varela E, et al: Statin-induced inhibition of MCF-7 breast cancer cell proliferation is related to cell cycle arrest and apoptotic and necrotic cell death mediated by an enhanced oxidative stress. Cancer Invest 26: 698-707, 2008.
18. Saito A, Saito N, Mol W, et al: Simvastatin inhibits growth via apoptosis and the induction of cell cycle arrest in human melanoma cells. Melanoma Res 18: 85-94, 2008.
19. Kulawiec M, Owens KM and Singh KK: Cancer cell mitochondria confer apoptosis resistance and promote metastasis. Cancer Biol Ther 8: 1378-1385, 2009.
20. Glinsky GV, Glinsky VV, Ivanova AB and Hueser CJ: Apoptosis and metastasis: increased apoptosis resistance of metastatic cancer cells is associated with the profound deficiency of apoptosis execution mechanisms. Cancer Lett 115: 185-193, 1997.
21. Herman-Antosiewicz A and Singh SV: Signal transduction pathways leading to cell cycle arrest and apoptosis induction in cancer cells by Allium vegetable-derived organosulfur compounds: a review. Mutat Res 555: 121-131, 2004. (Pubitemid 39345401)
22. Hindler K, Cleeland CS, Rivera E and Collard CD: The role of statins in cancer therapy. Oncologist 11: 306-315, 2006.
23. Cafforio P, Dammacco F, Gernone A and Silvestris F: Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells. Carcinogenesis 26: 883-891, 2005. (Pubitemid 41214316)
24. Aberg M, Wickstrom M and Siegbahn A: Simvastatin induces apoptosis in human breast cancer cells in a NFkappaB-dependent manner and abolishes the anti-apoptotic signaling of TF/FVIIa and TF/FVIIa/FXa. Thromb Res 122: 191-202, 2008. (Pubitemid 351754915)
25. Li HY, Appelbaum FR, Willman CL, Zager RA and Banker DE: Cholesterol-modulating agents kill acute myeloid leukemia cells and sensitize them to therapeutics by blocking adaptive cholesterol responses. Blood 101: 3628-3634, 2003.
26. Zhuang L, Kim J, Adam RM, Solomon KR and Freeman MR: Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. J Clin Invest 115: 959-968, 2005. (Pubitemid 40489400)
27. Gliemroth J, Zulewski H, Arnold H and Terzis AJ: Migration, proliferation, and invasion of human glioma cells following treatment with simvastatin. Neurosurg Rev 26: 117-124, 2003. (Pubitemid 36735735)
28. Paragh G, Kertai P, Kovacs P, Paragh G Jr, Fulop P and Foris G: HMG CoA reductase inhibitor fluvastatin arrests the development of implanted hepatocarcinoma in rats. Anticancer Res 23: 3949-3954, 2003. (Pubitemid 37474348)
29. Taras D, Blanc JF, Rullier A, et al: Pravastatin reduces lung metastasis of rat hepatocellular carcinoma via a coordinated decrease of MMP expression and activity. J Hepatol 46: 69-76, 2007. (Pubitemid 44834427)
30. Kawata S, Kakimoto H, Ishiguro H, Yamasaki E, Inui Y and Matsuzawa Y: Effect of pravastatin, a potent 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, on survival of AH130 hepatoma-bearing rats. Jpn J Cancer Res 83: 1120-1123, 1992. (Pubitemid 23009029)
31. Graf H, Jungst C, Straub G, et al: Chemoembolization combined with pravastatin improves survival in patients with hepatocellular carcinoma. Digestion 78: 34-38, 2008.
32. Kawata S, Yamasaki E, Nagase T, et al: Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial. Br J Cancer 84: 886-891, 2001. (Pubitemid 32385829)
33. Lee J, Jung KH, Park YS, et al: Simvastatin plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first-line chemotherapy in metastatic colorectal patients: a multicenter phase II study. Cancer Chemother Pharmacol 64: 657-663, 2009.
34. Murray AW: Recycling the cell cycle: cyclins revisited. Cell 116: 221-234, 2004.
35. Grana X and Reddy EP: Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 11: 211-219, 1995.
36. Pavletich NP: Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. J Mol Biol 287: 821-828, 1999.
37. Kastan MB, Canman CE and Leonard CJ: P53, cell cycle control and apoptosis: implications for cancer. Cancer Metastasis Rev 14: 3-15, 1995.
38. Molinari M: Cell cycle checkpoints and their inactivation in human cancer. Cell Prolif 33: 261-274, 2000.
39. Hoque A, Chen H and Xu XC: Statin induces apoptosis and cell growth arrest in prostate cancer cells. Cancer Epidemiol Biomarkers Prev 17: 88-94, 2008. (Pubitemid 351196277)
40. Denoyelle C, Albanese P, Uzan G, et al: Molecular mechanism of the anti-cancer activity of cerivastatin, an inhibitor of HMG-CoA reductase, on aggressive human breast cancer cells. Cell Signal 15: 327-338, 2003. (Pubitemid 36071677)
41. Teoh N, Pyakurel P, Dan YY, et al: Induction of p53 Renders ATM-Deficient Mice Refractory to Hepatocarcinogenesis. Gastroenterology 138: 1155-1165, 2010.
42. Chan KC, Wang CJ, Ho HH, Chen HM and Huang CN: Simvastatin inhibits cell cycle progression in glucose-stimulated proliferation of aortic vascular smooth muscle cells by upregulating cyclin dependent kinase inhibitors and p53. Pharmacol Res 58: 247-256, 2008.