Statins: A New Hope for Cancer Therapy

Ahmed Mohammed Kabel^1,

¹Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt

Cite this paper:
Ahmed Mohammed Kabel. Statins: A New Hope for Cancer Therapy. Journal of Cancer Research and Treatment. 2013; 1(2):36-38. doi: 10.12691/jcrt-1-2-3

Abstract

3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase is the key enzyme in cholesterol synthesis. Statins are used in treatment of hypercholesterolemia as inhibitors of HMG-CoA reductase. Cancer cells overexpress HMG-CoA reductase enzyme. Recent studies have demonstrated that statins may inhibit the proliferation of human breast cancer cells. Statins have proangiogenic effects in low therapeutic concentrations and angiostatic effects in higher concentrations. Statins induce apoptosis and reduce cell invasiveness in various cell lines, including malignant glioma, neuroblastoma and myeloid leukemia. The chemopreventive activity of statins against cancer is suggested to depend on inhibition of cholesterol synthesis together with their antioxidant and anti-inflammatory properties.

Keywords:
cholesterol statins cancer HMG-CoA

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Lewis LS. Statins are not bad medicine but their misuse is. BMJ 2013; 346:f4046.
[2]	Taylor F, Ward K, Moore TH et al. Statins for the primary prevention of cardiovascular disease". In Taylor, Fiona. Cochrane Database Syst Rev 2011; 1: CD004816.
[3]	lsheikh-Ali AA, Maddukuri PV, Han H, Karas RH. Effect of the Magnitude of Lipid Lowering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer: Insights From Large Randomized Statin Trials. Journal of the American College of Cardiology 2007; 50 (5): 409-418.
[4]	Boudreau DM, Yu O, Johnson J. Statin use and cancer risk: a comprehensive review. Expert Opin Drug Saf 2010; 9: 603-21.
[5]	Ahern TP, Pedersen L, Tarp M, et al. Statin prescriptions and breast cancer recurrence risk: a Danish nationwide prospective cohort study. J Natl Cancer Inst 2011; 103: 1461-8.
[6]	Dale KM, Coleman CI, Henyan NN, Kluger J, White CM. Statins and cancer risk: a meta-analysis. JAMA 2006; 295 (1): 74-80.
[7]	Poynter JN, Gruber SB, Higgins PD, Almog R, Bonner JD, Rennert HS, Low M, Greenson JK, Rennert G. Statins and the risk of colorectal cancer. N Engl J Med 2005; 352 (21): 2184-92.
[8]	Liu H, Ning Y, Chen C, Wang D. Effect of atorvastatin on tumor growth and metastasis in a breast cancer cell xenograft model and its mechanism. Front Med China 2009; 3: 443-446.
[9]	Wali VB, Bachawal SV, Sylvester PW. Suppression in Mevalonate Synthesis Mediates Antitumour Effects of Combined Statin and c-Tocotrienol Treatment. Lipids 2009; 44: 925-934.
[10]	Yang Z, Lee MJ, Zhao Y, Yang CS. Metabolism of tocotrienols in animals and synergistic inhibitory actions of tocotrienols with atorvastatin in cancer cells. Genes Nutr 2012; 7: 11-18.
[11]	Garwood ER, Kumar AS, Baehner FL, Moore DH, Au A, Hylton N, Flowers CI, Garber J, Lesnikoski BA, Hwang ES, Olopade O, Port ER, Campbell M, Esserman LJ. Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer. Breast Cancer Res Treat 2010; 119:137-144.
[12]	Tsan, YT, Lee CH, Wang JD, Chen PC. Statins and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection. J Clin Oncol 2012; 30: 623-630.
[13]	Bernini F, Poli A, Paoletti R. Safety of HMG-CoA Reductase Inhibitors: Focus on Atorvastatin. Cardiovascular Drugs and Therapy 2001; 15: 211-218.
[14]	Huang EH, Johnson LA, Eaton K, Hynes MJ, Carpentino JE, Higgins P. Atorvastatin induces apoptosis in vitro and slows growth of tumor xenografts but not polyp formation in min mice. Dig Dis Sci 2010; 55: 3086-3094.
[15]	Ghaisas M, Dandawate PR, Zawar SA, Ahire YS, Gandhi SP. Antioxidant, antinociceptive and anti-inflammatory activities of atorvastatin and rosuvastatin in various experimental models. Inflammopharmacol 2010; 18: 169-177.
[16]	Sugiyama M, Ohashi M, Takase H, Sato K, Ueda R, Dohi Y. Effects of atorvastatin on inflammation and oxidative stress. Heart Vessels 2005; 20: 133-136.
[17]	Emberson JR, Kearney PM, Blackwell L, et al. Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy. PloS One 2012;7(1):e29849.
[18]	Park HJ, Kong D, Iruela-Arispe L, Begley U, Tang D, Galper JB. 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors interfere with angiogenesis by inhibiting the geranylgeranylation of RhoA. Circ Res 2002; 91: 143-150.
[19]	Hindler K, Cleeland CS, Rivera E, Collard CD. The role of statins in cancer therapy. The Oncologist 2006; 11: 306-315.
[20]	Sutter AP, Maaser K, Höpfner M, Huether A, Schuppan D, Scherübl H. Cell cycle arrest and apoptosis induction in hepatocellular carcinoma cells by HMG-CoA reductase inhibitors. Synergistic antiproliferative action with ligands of the peripheral benzodiazepine receptor. J Hepatol 2005; 43(5): 808-16.
[21]	Nubel T, Dippold W, Kleinert H, Kaina B, Fritz G. Lovastatin inhibits Rho-regulated expression of E-selectin by TNF alpha and attenuates tumor cell adhesion. FASEB J 2004; 18: 140-142.
[22]	Collisson EA, Kleer C, Wu M, De A, Gambhir SS, Merajver SD, Kolodney MS. Atorvastatin prevents RhoC isoprenylation, invasion, and metastasis in human melanoma cells. Mol Cancer Ther 2003; 2: 941-948.
[23]	Kabel AM, Abdel-Rahman MN, El-Sisi Ael-D, Haleem MS, Ezzat NM, El Rashidy MA. Effect of atorvastatin and methotrexate on solid Ehrlich tumor. Eur J Pharmacol 2013; 713(1-3):47-53.
[24]	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: 2223-2229.
[25]	Xu HW, Xu L, Hao JH, Qin CY, Liu H. Expression of P-glycoprotein and multidrug resistance-associated protein is associated with multidrug resistance in gastric cancer. J Int Med Res 2010; 38: 34-42.
[26]	Feleszko W, Mlynarczuk I, Olszewska D, Jalili A, Grzela T, Lasek W, Hoser G, Korczak-Kowalska G, Jakóbisiak M. Lovastatin potentiates antitumour activity of doxorubicin in murine melanoma via an apoptosis dependent mechanism. Int J Cancer 2002; 100: 111-118.