Lovastatin lactone elicits human lung cancer cell apoptosis via a COX-2/PPARγ-dependent pathway

Oncotarget

Volumn 7, Issue 9, 2016, Pages 10345-10362

  Walther, Udo ^a   Emmrich, Kristin ^a   Ramer, Robert ^a   Mittag, Nadine ^a   Hinz, Burkhard ^a  

^a ROSTOCK UNIVERSITY MEDICAL CENTER   (Germany)

Author keywords

Apoptosis; Cyclooxygenase 2; Human lung cancer cells; Lovastatin lactone; Peroxisome proliferator activated receptor

Indexed keywords

15 DEOXY DELTA12,14 PROSTAGLANDIN J2; 2 CHLORO 5 NITROBENZANILIDE; CYCLOOXYGENASE 2; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOVASTATIN LACTONE; MESSENGER RNA; MEVALONIC ACID; MEVINOLIN; N (2 CYCLOHEXYLOXY 4 NITROPHENYL)METHANESULFONAMIDE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; 2-CHLORO-5-NITROBENZANILIDE; 9-DEOXY-DELTA-9-PROSTAGLANDIN D2; ANILIDE; CYCLOOXYGENASE 2 INHIBITOR; N-(2-CYCLOHEXYLOXY-4-NITROPHENYL)METHANESULFONAMIDE; NITROBENZENE DERIVATIVE; PROSTAGLANDIN D2; PTGS2 PROTEIN, HUMAN; SULFONAMIDE;

A549 CELL LINE; APOPTOSIS; ARTICLE; CELL NUCLEUS; CELL VIABILITY; CELLULAR DISTRIBUTION; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOSOL; DNA FRAGMENTATION; HUMAN; HUMAN CELL; LUNG CANCER CELL LINE; PROSTAGLANDIN SYNTHESIS; UPREGULATION; A-549 CELL LINE; ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; CELL SURVIVAL; DRUG EFFECTS; GENETICS; LUNG NEOPLASMS; METABOLISM; PATHOLOGY; RNA INTERFERENCE; TUMOR CELL LINE;

A549 CELLS; ANILIDES; APOPTOSIS; CELL LINE, TUMOR; CELL SURVIVAL; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITORS; DNA FRAGMENTATION; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; LOVASTATIN; LUNG NEOPLASMS; NITROBENZENES; PPAR GAMMA; PROSTAGLANDIN D2; RNA INTERFERENCE; RNA, MESSENGER; RNA, SMALL INTERFERING; SULFONAMIDES;

EID: 84961654842     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.7213     Document Type: Article

References (56)

1. Hamelin BA, Turgeon J. Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci. 1998; 19: 26-37
2. Brown AJ. Cholesterol, statins and cancer. Clin Exp Pharmacol Physiol. 2007; 34: 135-141
3. Lovastatin Study Groups I Through IV. Lovastatin 5-Year Safety and Efficacy Study. Arch Intern Med. 1993; 153: 1079-1087
4. Blais L, Desgagné A, LeLorier J. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and the risk of cancer: a nested case-control study. Arch Intern Med. 2000; 160: 2363-2368
5. Pedersen TR, Wilhelmsen L, Faergeman O, Strandberg TE, Thorgeirsson G, Troedsson L, Kristianson J, Berg K, Cook TJ, Haghfelt T, Kjekshus J, Miettinen T, Olsson AG, et al. Follow-up study of patients randomized in the Scandinavian simvastatin survival study (4S) of cholesterol lowering. Am J Cardiol. 2000; 86: 257-262
6. Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Engl J Med. 2012; 367: 1792-1802
7. Khurana V, Bejjanki HR, Caldito G, Owens MW. Statins reduce the risk of lung cancer in humans: a large casecontrol study of US veterans. Chest. 2007; 131: 1282-1288
8. Sumi S, Beauchamp RD, Townsend CM Jr, Uchida T, Murakami M, Rajaraman S, Ishizuka J, Thompson JC. Inhibition of pancreatic adenocarcinoma cell growth by lovastatin. Gastroenterology. 1992; 103: 982-989
9. Hawk MA, Cesen KT, Siglin JC, Stoner GD, Ruch RJ. Inhibition of lung tumor cell growth in vitro and mouse lung tumor formation by lovastatin. Cancer Lett. 1996; 109: 217-222
10. Dimitroulakos J, Ye LY, Benzaquen M, Moore MJ, Kamel-Reid S, Freedman MH, Yeger H, Penn LZ. Differential sensitivity of various pediatric cancers and squamous cell carcinomas to lovastatin-induced apoptosis: therapeutic implications. Clin Cancer Res. 2001; 7: 158-167
11. Cafforio P, Dammacco F, Gernone A, Silvestris F. Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells. Carcinogenesis. 2005; 26: 883-891
12. Kusama T, Mukai M, Iwasaki T, Tatsuta M, Matsumoto Y, Akedo H, Nakamura H. Inhibition of epidermal growth factor-induced RhoA translocation and invasion of human pancreatic cancer cells by 3-hydroxy-3-methylglutarylcoenzyme a reductase inhibitors. Cancer Res. 2001; 61: 4885-4891
13. Kaminski R, Kozar K, Kopec M, Basak G, Skierski JS, Koronkiewicz M, Jakobisiak M, Golab J. Discussion on 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis. Gastroenterology. 2002; 123: 1747
14. Kusama T, Mukai M, Iwasaki T, Tatsuta M, Matsumoto Y, Akedo H, Inoue M, Nakamura H. 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis. Gastroenterology. 2002; 122: 308-317
15. Frick M, Dulak J, Cisowski J, Józkowicz A, Zwick R, Alber H, Dichtl W, Schwarzacher SP, Pachinger O, Weidinger F. Statins differentially regulate vascular endothelial growth factor synthesis in endothelial and vascular smooth muscle cells. Atherosclerosis. 2003; 170: 229-236
16. Depasquale I, Wheatley DN. Action of Lovastatin (Mevinolin) on an in vitro model of angiogenesis and its co-culture with malignant melanoma cell lines. Cancer Cell Int. 2006; 6: 9
17. Zhao TT, Trinh D, Addison CL, Dimitroulakos J. Lovastatin inhibits VEGFR and AKT activation: synergistic cytotoxicity in combination with VEGFR inhibitors. PLoS One. 2010; 5: e12563
18. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arteriosclerosis Thromb Vasc Biol. 2001; 21: 1712-1719
19. Bondar VM, Sweeney-Gotsch B, Andreeff M, Mills GB, McConkey DJ. Inhibition of the phosphatidylinositol 3'-kinase-AKT pathway induces apoptosis in pancreatic carcinoma cells in vitro and in vivo. Mol Cancer Ther. 2002; 1: 989-997
20. Hall A. Rho GTPases and the actin cytoskeleton. Science. 1998; 279: 509-514
21. Rao S, Porter DC, Chen X, Herliczek T, Lowe M, Keyomarsi K. Lovastatin-mediated G1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase. Proc Natl Acad Sci U S A. 1999; 96: 7797-7802
22. Wójcik C, Bury M, Stoklosa T, Giermasz A, Feleszko W, Mlynarczuk I, Pleban E, Basak G, Omura S, Jakóbisiak M. Lovastatin and simvastatin are modulators of the proteasome. Int J Biochem Cell Biol. 2000; 32: 957-965
23. Efuet ET, Keyomarsi K. Farnesyl and geranylgeranyl transferase inhibitors induce G1 arrest by targeting the proteasome. Cancer Res. 2006; 66: 1040-1051
24. Munkarah AR, Genhai Z, Morris R, Baker VV, Deppe G, Diamond MP, Saed GM. Inhibition of paclitaxel-induced apoptosis by the specific COX-2 inhibitor, NS-398, in epithelial ovarian cancer cells. Gynecol Oncol. 2003; 88: 429-433
25. Na HK, Inoue H, Surh YJ. ET-18-O-CH3-induced apoptosis is causally linked to COX-2 upregulation in H-ras transformed human breast epithelial cells. FEBS Lett. 2005; 579: 62-87
26. Eichele K, Ramer R, Hinz B. Decisive role of cyclooxygenase-2 and lipocalin-type prostaglandin D synthase in chemotherapeutics-induced apoptosis of human cervical carcinoma cells. Oncogene. 2008; 27: 3032-3044
27. Elrod HA, Yue P, Khuri FR, Sun SY. Celecoxib antagonizes perifosine's anticancer activity involving a cyclooxygenase-2-dependent mechanism. Mol Cancer Ther. 2009; 8: 2575-2585
28. Hinz B, Ramer R, Eichele K, Weinzierl U, Brune K. Upregulation of cyclooxygenase-2 expression is involved in R(+)-methanandamide-induced apoptotic death of human neuroglioma cells. Mol Pharmacol. 2004; 66; 1643-1651
29. Eichele K, Ramer R, Hinz B. R(+)-methanandamideinduced apoptosis of human cervical carcinoma cells involves a cyclooxygenase-2-dependent pathway. Pharm Res. 2009; 26: 346-355
30. Kuc C, Jenkins A, Van Dross RT. Arachidonoyl ethanolamide (AEA)-induced apoptosis is mediated by J-series prostaglandins and is enhanced by fatty acid amide hydrolase (FAAH) blockade. Mol Carcinog. 2012; 51: 139-149
31. Ramer R, Heinemann K, Merkord J, Rohde H, Salamon A, Linnebacher M, Hinz B. Cyclooxygenase-2 and peroxisome proliferator activated receptor gamma confer cannabidiolinduced apoptosis of human lung cancer cells. Mol Cancer Ther. 2013; 12: 69-82
32. Maccarrone M, Pauselli R, Di Rienzo M, Finazzi-Agrò A. 2002. Binding, degradation and apoptotic activity of stearoylethanolamide in rat C6 glioma cells. Biochem J. 2002; 366: 137-144
33. Ramer R, Walther U, Borchert P, Laufer S, Linnebacher M, Hinz B. Induction but not inhibition of COX-2 confers human lung cancer cell apoptosis by celecoxib. J Lipid Res. 2013; 54: 3116-3129
34. Clay CE, Namen AM, Atsumi G, Willingham MC, High HP, Kute TE, Trimboli AJ, Fonteh AN, Dawson PA, Chilton FH. Influence of J series prostaglandins on apoptosis and tumorigenesis of breast cancer cells. Carcinogenesis. 1999; 20: 1905-1911
35. Na HK, Surh YJ. Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands as bifunctional regulators of cell proliferation. Biochem Pharmacol. 2003; 66: 1381-1391
36. Kim J, Yang P, Suraokar M, Sabichi AL, Llansa ND, Mendoza G, Subbarayan V, Logothetis CJ, Newman RA, Lippman SM, Menter DG. Suppression of prostate tumor cell growth by stromal cell prostaglandin D synthasederived products. Cancer Res. 2005; 65: 6189-6198
37. Degraeve F, Bolla M, Blaie S, Créminon C, Quére I, Boquet P, Lévy-Toledano S, Bertoglio J, Habib A. Modulation of COX-2 expression by statins in human aortic smooth muscle cells. J Biol Chem. 2001; 276: 46849-46855
38. Chen JC, Huang KC, Wingerd B, Wu WT, Lin WW. HMGCoA reductase inhibitors induce COX-2 gene expression in murine macrophages: role of MAPK cascades and promoter elements for CREB and C/EBPβ. Exp Cell Res. 2004; 301: 305-319
39. Habib A, Shamseddeen I, Nasrallah MS, Antoun TA, Nemer G, Bertoglio J, Badreddine R, Badr KF. Modulation of COX-2 expression by statins in human monocytic cells. FASEB J. 2007; 21: 1665-1674
40. Yano M, Matsumura T, Senokuchi T, Ishii N, Murata Y, Taketa K, Motoshima H, Taguchi T, Sonoda K, Kukidome D, Takuwa Y, Kawada T, Brownlee M, et al. Statins activate peroxisome proliferator-activated receptor γ through extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase-dependent cycloogygenase-2 expression in macrophages. Circ Res. 2007; 100: 1442-1451
41. Shibuya A, Wada K, Nakajima A, Saeki M, Katayama K, Mayumi T, Kadowaki T, Niwa H, Kamisaki Y. Nitration of PPARγ inhibits ligand-dependent translocation into the nucleus in a macrophage-like cell line, RAW 264. FEBS Lett. 2002; 525: 43-47
42. Rousseaux C, Lefebvre B, Dubuquoy L, Lefebvre P, Romano O, Auwerx J, Metzger D, Wahli W, Desvergne B, Naccari GC, Chavatte P, Farce A, Bulois P, et al. Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator-activated receptorgamma. J Exp Med. 2005; 201: 1205-1215
43. Bocca C, Bozzo F, Francica S, Colombatto S, Maglietta A. Involvement of PPARγ and E-cadherin/beta-catenin pathway in the antiproliferative effect of conjugated linoleic acid in MCF-7 cells. Int J Cancer. 2007; 121: 248-256
44. Bucher M, Mair G, Kees F. Effect of roxithromycin on the pharmacokinetics of lovastatin in volunteers. Eur J Clin Pharmacol. 2002; 57: 787-791
45. Holstein SA, Knapp HR, Clamon GH, Murry DJ, Hohl RJ. Pharmacodynamic effects of high dose lovastatin in subjects with advanced malignancies. Cancer Chemother Pharmacol. 2006; 57: 155-164
46. Liu WM, Joel SP. The schedule-dependent effects of etoposide in leukaemic cell lines: a function of concentration and duration. Cancer Chemother Pharmacol. 2003; 51: 291-296
47. Grösch S, Maier TJ, Schiffmann S, Geisslinger G. Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors. J Natl Cancer Inst. 2006; 98: 736-747
48. Rockwell P, Yuan H, Magnusson R, Figueiredo-Pereira ME. Proteasome inhibition in neuronal cells induces a proinflammatory response manifested by upregulation of cyclooxygenase-2, its accumulation as ubiquitin conjugates, and production of the prostaglandin PGE2. Arch Biochem Biophys. 2000; 374: 325-333
49. Chen JJ, Huang WC, Chen CC. Transcriptional regulation of cyclooxygenase-2 in response to proteasome inhibitors involves reactive oxygen species-mediated signaling pathway and recruitment of CCAAT/enhancer-binding protein delta and CREB-binding protein. Mol Biol Cell. 2005; 16: 5579-5591
50. Kumar B, Andreatta C, Koustas WT, Cole WC, Edwards-Prasad J, Prasad KN. Mevastatin induces degeneration and decreases viability of cAMP-induced differentiated neuroblastoma cells in culture by inhibiting proteasome activity, and mevalonic acid lactone prevents these effects. J Neurosci Res. 2002; 68: 627-635
51. Dimitroulakos J, Ye LY, Benzaquen M, Moore MJ, Kamel-Reid S, Freedman MH, Yeger H, Penn LZ. Differential sensitivity of various pediatric cancers and squamous cell carcinomas to lovastatin-induced apoptosis: therapeutic implications. Clin Cancer Res. 2001; 7: 158-167
52. Serajuddin AT, Ranadive SA, Mahoney EM. Relative lipophilicities, solubilities, and structure-pharmacological considerations of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors pravastatin, lovastatin, mevastatin, and simvastatin. J Pharm Sci. 1991; 80: 830-834
53. Nezasa K, Higaki K, Takeuchi M, Nakano M, Koike M. Uptake of rosuvastatin by isolated rat hepatocytes: comparison with pravastatin. Xenobiotica. 2003; 33: 379-388
54. Pan HY, DeVault AR, Wang-Iverson D, Ivashkiv E, Swanson BN, Sugerman AA. Comparative pharmacokinetics and pharmacodynamics of pravastatin and lovastatin. J Clin Pharmacol. 1990; 30: 1128-1135
55. Todd PA, Goa KL. Simvastatin. A review of its pharmacological properties and therapeutic potential in hypercholesterolaemia. Drugs. 1990; 40: 583-607
56. Mauro VF. Clinical pharmacokinetics and practical applications of simvastatin. Clin Pharmacokinet. 1993; 24: 195-202