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A lipophilic statin, pitavastatin, suppresses inflammation-associated mouse colon carcinogenesis

  1. Yumiko Yasui1,
  2. Rikako Suzuki1,
  3. Shingo Miyamoto2,
  4. Tetsuya Tsukamoto3,
  5. Shigeyuki Sugie1,
  6. Hiroyuki Kohno1,
  7. Takuji Tanaka1,†,*

Article first published online: 26 JUL 2007

DOI: 10.1002/ijc.22976

Issue

International Journal of Cancer

International Journal of Cancer

Volume 121, Issue 10, pages 2331–2339, 15 November 2007

Additional Information

How to Cite

Yasui, Y., Suzuki, R., Miyamoto, S., Tsukamoto, T., Sugie, S., Kohno, H. and Tanaka, T. (2007), A lipophilic statin, pitavastatin, suppresses inflammation-associated mouse colon carcinogenesis. Int. J. Cancer, 121: 2331–2339. doi: 10.1002/ijc.22976

Author Information

  1. 1

    Department of Oncologic Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan

  2. 2

    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan

  3. 3

    Division of Oncological Pathology, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan

  1. †

    Fax: +81-76-286-6926.

*Department of Oncologic Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan

Publication History

  1. Issue published online: 25 SEP 2007
  2. Article first published online: 26 JUL 2007
  3. Manuscript Accepted: 6 JUN 2007
  4. Manuscript Received: 9 APR 2007

Funded by

  • Ministry of Education, Culture, Sports, Science and Technology of Japan (Grants-in-Aid for Scientific Research). Grant Numbers: 152052, 00120029, 18592076
  • Kanazawa Medical University. Grant Numbers: H2006-6, C2006-3
  • Ministry of Health, Labour and Welfare of Japan (Grant-in-Aid for Cancer Research and a Grant-in-Aid for the 3rd Term for a Comprehensive 10-year Strategy for Cancer Control)

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References

  • 1
    Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ, for the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333: 1301–7.
  • 2
    Collins R, Armitage J, Parish S, Sleigh P, Peto R. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003; 361: 2005–16.
  • 3
    Saito Y, Yamada N, Teramoto T, Itakura H, Hata Y, Nakaya N, Mabuchi H, Tushima M, Sasaki J, Goto Y, Ogawa N. Clinical efficacy of pitavastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in patients with hyperlipidemia. Dose-finding study using the double-blind, three-group parallel comparison. Arzneimittelforschung 2002; 52: 251–5.
  • 4
    Streja L, Packard CJ, Shepherd J, Cobbe S, Ford I. Factors affecting low-density lipoprotein and high-density lipoprotein cholesterol response to pravastatin in the West of Scotland Coronary Prevention Study (WOSCOPS). Am J Cardiol 2002; 90: 731–6.
  • 5
    Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet 2000; 356: 1627–31.
  • 6
    Crisby M. The role of pleiotropic effects of statins in dementia. Acta Neurol Scand Suppl 2006; 185: 115–18.
    Direct Link:
  • 7
    Meier CR, Schlienger RG, Kraenzlin ME, Schlegel B, Jick H. HMG-CoA reductase inhibitors and the risk of fractures. JAMA 2000; 283: 3205–10.
  • 8
    Graaf MR, Richel DJ, van Noorden CJ, Guchelaar HJ. Effects of statins and farnesyltransferase inhibitors on the development and progression of cancer. Cancer Treat Rev 2004; 30: 609–41.
  • 9
    Chan KK, Oza AM, Siu LL. The statins as anticancer agents. Clin Cancer Res 2003; 9: 10–19.
  • 10
    Jakobisiak M, Golab J. Potential antitumor effects of statins. Int J Oncol 2003; 23: 1055–69.
  • 11
    Campbell MJ, Esserman LJ, Zhou Y, Shoemaker M, Lobo M, Borman E, Baehner F, Kumar AS, Adduci K, Marx C, Petricoin EF, Liotta LA, et al. Breast cancer growth prevention by statins. Cancer Res 2006; 66: 8707–14.
  • 12
    Demierre MF, Higgins PD, Gruber SB, Hawk E, Lippman SM. Statins and cancer prevention. Nat Rev Cancer 2005; 5: 930–42.
  • 13
    Narisawa T, Fukaura Y, Terada K, Umezawa A, Tanida N, Yazawa K, Ishikawa C. Prevention of 1,2-dimethylhydrazine-induced colon tumorigenesis by HMG-CoA reductase inhibitors, pravastatin and simvastatin, in ICR mice. Carcinogenesis 1994; 15: 2045–8.
  • 14
    Narisawa T, Morotomi M, Fukaura Y, Hasebe M, Ito M, Aizawa R. Chemoprevention by pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, of N-methyl-N-nitrosourea-induced colon carcinogenesis in F344 rats. Jpn J Cancer Res 1996; 87: 798–804.
  • 15
    Reddy BS, Wang CX, Kong AN, Khor TO, Zheng X, Steele VE, Kopelovich L, Rao CV. Prevention of azoxymethane-induced colon cancer by combination of low doses of atorvastatin, aspirin, and celecoxib in F 344 rats. Cancer Res 2006; 66: 4542–6.
  • 16
    Swamy MV, Patlolla JM, Steele VE, Kopelovich L, Reddy BS, Rao CV. Chemoprevention of familial adenomatous polyposis by low doses of atorvastatin and celecoxib given individually and in combination to APCMin mice. Cancer Res 2006; 66: 7370–7.
  • 17
    Pleiner J, Schaller G, Mittermayer F, Zorn S, Marsik C, Polterauer S, Kapiotis S, Wolzt M. Simvastatin prevents vascular hyporeactivity during inflammation. Circulation 2004; 110: 3349–54.
  • 18
    Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 2001; 357: 539–45.
  • 19
    Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420: 860–7.
  • 20
    Rutter M, Saunders B, Wilkinson K, Rumbles S, Schofield G, Kamm M, Williams C, Price A, Talbot I, Forbes A. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology 2004; 126: 451–9.
  • 21
    Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001; 48: 526–35.
  • 22
    Tanaka T, Kohno H, Suzuki R, Yamada Y, Sugie S, Mori H. A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate. Cancer Sci 2003; 94: 965–73.
    Direct Link:
  • 23
    Kohno H, Suzuki R, Curini M, Epifano F, Maltese F, Gonzales SP, Tanaka T. Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice. Int J Cancer 2006; 118: 2936–42.
    Direct Link:
  • 24
    Hata K, Tanaka T, Kohno H, Suzuki R, Qiang SH, Kuno T, Hirose Y, Hara A, Mori H. Lack of enhancing effects of degraded λ-carrageenan on the development of β-catenin-accumulated crypts in male DBA/2J mice initiated with azoxymethane. Cancer Lett 2006; 238: 69–75.
  • 25
    Mukhtar RY, Reid J, Reckless JP. Pitavastatin. Int J Clin Pract 2005; 59: 239–4.
    Direct Link:
  • 26
    Flores NA. Pitavastatin Nissan/Kowa Yakuhin/Novartis/Sankyo. Curr Opin Investig Drugs 2002; 3: 1334–41.
  • 27
    Saito Y, Yamada N, Teramoto T, Itakura H, Hata Y, Nakaya N, Mabuchi H, Tushima M, Sasaki J, Ogawa N, Goto Y. A randomized, double-blind trial comparing the efficacy and safety of pitavastatin versus pravastatin in patients with primary hypercholesterolemia. Atherosclerosis 2002; 162: 373–9.
  • 28
    Iglesias P, Diez JJ. New drugs for the treatment of hypercholesterolaemia. Expert Opin Investig Drugs 2003; 12: 1777–89.
  • 29
    Kajinami K, Takekoshi N, Saito Y. Pitavastatin: efficacy and safety profiles of a novel synthetic HMG-CoA reductase inhibitor. Cardiovasc Drug Rev 2003; 21: 199–215.
    Direct Link:
  • 30
    Morikawa S, Takabe W, Mataki C, Kanke T, Itoh T, Wada Y, Izumi A, Saito Y, Hamakubo T, Kodama T. The effect of statins on mRNA levels of genes related to inflammation, coagulation, and vascular constriction in HUVEC. Human umbilical vein endothelial cells. J Atheroscler Thromb 2002; 9: 178–3.
  • 31
    Chan EP, Lichtenstein GR. Chemoprevention: risk reduction with medical therapy of inflammatory bowel disease. Gastroenterol Clin North Am 2006; 35: 675–712.
  • 32
    Mutoh M, Niho N, Wakabayashi K. Concomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice. Biol Chem 2006; 387: 381–5.
  • 33
    Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 1993; 69: 238–49.
  • 34
    Rea WE, Durrant DC, Boldy DA. Ulcerative colitis after statin treatment. Postgrad Med J 2002; 78: 286–7.
  • 35
    Skaletz-Rorowski A, Walsh K. Statin therapy and angiogenesis. Curr Opin Lipidol 2003; 14: 599–603.
  • 36
    Crisby M. Modulation of the inflammatory process by statins. Drugs Today (Barc) 2003; 39: 137–43.
  • 37
    Devaraj S, Rogers J, Jialal I. Statins and biomarkers of inflammation. Curr Atheroscler Rep 2007; 9: 33–41.
  • 38
    Lee JY, Kim JS, Kim JM, Kim N, Jung HC, Song IS. Simvastatin inhibits NF-κB signaling in intestinal epithelial cells and ameliorates acute murine colitis. Int Immunopharmacol 2007; 7: 241–8.
  • 39
    Naito Y, Katada K, Takagi T, Tsuboi H, Isozaki Y, Handa O, Kokura S, Yoshida N, Ichikawa H, Yoshikawa T. Rosuvastatin, a new HMG-CoA reductase inhibitor, reduces the colonic inflammatory response in dextran sulfate sodium-induced colitis in mice. Int J Mol Med 2006; 17: 997–1004.
  • 40
    Fujino M, Miura S, Matsuo Y, Tanigawa H, Kawamura A, Saku K. Pitavastatin-induced down-regulation of CCR2 and CCR5 in monocytes is associated with the arrest of cell-cycle in S phase. Atherosclerosis 2006; 187: 301–8.
  • 41
    Papadakis KA. Chemokines in inflammatory bowel disease. Curr Allergy Asthma Rep 2004; 4: 83–9.
  • 42
    Wang J, Tokoro T, Matsui K, Higa S, Kitajima I. Pitavastatin at low dose activates endothelial nitric oxide synthase through PI3K-AKT pathway in endothelial cells. Life Sci 2005; 76: 2257–68.
  • 43
    Procko E, McColl SR. Leukocytes on the move with phosphoinositide 3-kinase and its downstream effectors. Bioessays 2005; 27: 153–63.
    Direct Link:
  • 44
    Blume-Jensen P, Hunter T. Oncogenic kinase signalling. Nature 2001; 411: 355–65.
  • 45
    Luo J, Manning BD, Cantley LC. Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell 2003; 4: 257–62.
  • 46
    Rychahou PG, Jackson LN, Silva SR, Rajaraman S, Evers BM. Targeted molecular therapy of the PI3K pathway: therapeutic significance of PI3K subunit targeting in colorectal carcinoma. Ann Surg 2006; 243: 833–42.
  • 47
    Kankuri E, Hamalainen M, Hukkanen M, Salmenpera P, Kivilaakso E, Vapaatalo H, Moilanen E. Suppression of pro-inflammatory cytokine release by selective inhibition of inducible nitric oxide synthase in mucosal explants from patients with ulcerative colitis. Scand J Gastroenterol 2003; 38: 186–92.
  • 48
    Halliwell B. What nitrates tyrosine? Is nitrotyrosine specific as a biomarker of peroxynitrite formation in vivo? FEBS Lett 1997; 411: 157–60.
  • 49
    Ambs S, Merriam WG, Bennett WP, Felley-Bosco E, Ogunfusika MO, Oser SM, Klein S, Shields PG, Billiar TR, Harris CC. Frequent nitric oxide synthase-2 expression in human colon adenomas: implication for tumor angiogenesis and colon cancer progression. Cancer Res 1998; 58: 334–41.
  • 50
    Takahashi M, Mutoh M, Kawamori T, Sugimura T, Wakabayashi K. Altered expression of β-catenin, inducible nitric oxide synthase and cyclooxygenase-2 in azoxymethane-induced rat colon carcinogenesis. Carcinogenesis 2000; 21: 1319–27.
  • 51
    Barnes PJ, Karin M. Nuclear factor-κB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 1997; 336: 1066–71.
  • 52
    Chen C, Edelstein LC, Gelinas C. The Rel/NF-κB family directly activates expression of the apoptosis inhibitor Bcl-x(L). Mol Cell Biol 2000; 20: 2687–95.
  • 53
    Barkett M, Gilmore TD. Control of apoptosis by Rel/NF-κB transcription factors. Oncogene 1999; 18: 6910–24.
  • 54
    Wang J, Tokoro T, Higa S, Kitajima I. Anti-inflammatory effect of pitavastatin on NF-κB activated by TNF-α in hepatocellular carcinoma cells. Biol Pharm Bull 2006; 29: 634–9.
  • 55
    Garat C, Arend WP. Intracellular IL-1Ra type 1 inhibits IL-1-induced IL-6 and IL-8 production in Caco-2 intestinal epithelial cells through inhibition of p38 mitogen-activated protein kinase and NF-κB pathways. Cytokine 2003; 23: 31–40.
  • 56
    Kibayashi E, Urakaze M, Kobashi C, Kishida M, Takata M, Sato A, Yamazaki K, Kobayashi M. Inhibitory effect of pitavastatin (NK-104) on the C-reactive-protein-induced interleukin-8 production in human aortic endothelial cells. Clin Sci (Lond) 2005; 108: 515–21.
  • 57
    Masamura K, Oida K, Kanehara H, Suzuki J, Horie S, Ishii H, Miyamori I. Pitavastatin-induced thrombomodulin expression by endothelial cells acts via inhibition of small G proteins of the Rho family. Arterioscler Thromb Vasc Biol 2003; 23: 512–17.
  • 58
    Davignon J, Mabile L. Mechanisms of action of statins and their pleiotropic effects (in French). Ann Endocrinol (Paris) 2001; 62 (Part 2): 101–12.
  • 59
    Agarwal B, Bhendwal S, Halmos B, Moss SF, Ramey WG, Holt PR. Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells. Clin Cancer Res 1999; 5: 2223–9.
  • 60
    Cafforio P, Dammacco F, Gernone A, Silvestris F. Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells. Carcinogenesis 2005; 26: 883–91.
  • 61
    Marcelli M, Cunningham GR, Haidacher SJ, Padayatty SJ, Sturgis L, Kagan C, Denner L. Caspase-7 is activated during lovastatin-induced apoptosis of the prostate cancer cell line LNCaP. Cancer Res 1998; 58: 76–83.
  • 62
    Wang IK, Lin-Shiau SY, Lin JK. Induction of apoptosis by lovastatin through activation of caspase-3 and DNase II in leukaemia HL-60 cells. Pharmacol Toxicol 2000; 86: 83–91.
  • 63
    Nagashima T, Okazaki H, Yudoh K, Matsuno H, Minota S. Apoptosis of rheumatoid synovial cells by statins through the blocking of protein geranylgeranylation: a potential therapeutic approach to rheumatoid arthritis. Arthritis Rheum 2006; 54: 579–86.
    Direct Link:
  • 64
    Tsujimoto A, Takemura G, Mikami A, Aoyama T, Ohno T, Maruyama R, Nakagawa M, Minatoguchi S, Fujiwara H. A therapeutic dose of the lipophilic statin pitavastatin enhances oxidant-induced apoptosis in human vascular smooth muscle cells. J Cardiovasc Pharmacol 2006; 48: 160–5.
  • 65
    Sivaprasad U, Abbas T, Dutta A. Differential efficacy of 3-hydroxy-3-methylglutaryl CoA reductase inhibitors on the cell cycle of prostate cancer cells. Mol Cancer Ther 2006; 5: 2310–16.
  • 66
    Maron DJ, Fazio S, Linton MF. Current perspectives on statins. Circulation 2000; 101: 207–13.
  • 67
    Tabuchi M, Kitayama J, Nagawa H. Hypertriglyceridemia is positively correlated with the development of colorectal tubular adenoma in Japanese men. World J Gastroenterol 2006; 12: 1261–4.
  • 68
    Yamada K, Araki S, Tamura M, Sakai I, Takahashi Y, Kashihara H, Kono S. Relation of serum total cholesterol, serum triglycerides and fasting plasma glucose to colorectal carcinoma in situ. Int J Epidemiol 1998; 27: 794–8.
  • 69
    Mutoh M, Akasu T, Takahashi M, Niho N, Yoshida T, Sugimura T, Wakabayashi K. Possible involvement of hyperlipidemia in increasing risk of colorectal tumor development in human familial adenomatous polyposis. Jpn J Clin Oncol 2006; 36: 166–71.
  • 70
    Kosaka T, Yoshino J, Inui K, Wakabayashi T, Okushima K, Kobayashi T, Miyoshi H, Nakamura Y, Hayashi S, Shiraishi T, Watanabe M, Yamamoto T et al. Impact of lipoprotein lipase gene polymorphisms on ulcerative colitis. World J Gastroenterol 2006; 12: 6325–30.
  • 71
    Itzkowitz SH. Cancer prevention in patients with inflammatory bowel disease. Gastroenterol Clin North Am 2002; 31: 1133–44.
  • 72
    Rubin DT, Parekh N. Colorectal cancer in inflammatory bowel disease: molecular and clinical considerations. Curr Treat Options Gastroenterol 2006; 9: 211–20.
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