Synergistic inhibitory effect of apomine and lovastatin on osteosarcoma cell growth

Osteosarcoma is the most frequent malignant primary bone tumor that occurs mainly in the young, with an incidence peak observed at age 18 years. Both apomine and lovastatin have antitumor activity in a variety of cancer cell lines. Apomine, a 1,1‐bisphosphonate‐ester, increases the rate of degradation of 3‐hydroxy‐3 methylglutaryl‐coenzyme A (HMG‐CoA) reductase, the rate‐limiting enzyme in the mevalonate pathway, whereas lovastatin competitively inhibits HMG‐CoA reductase enzyme activity, thereby preventing protein prenylation and cholesterol synthesis.

[1]  K. S. Hall,et al.  Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[2]  D. Heymann,et al.  Mifamurtide for the treatment of nonmetastatic osteosarcoma , 2011, Expert opinion on pharmacotherapy.

[3]  G. Moriceau,et al.  Zoledronic acid potentiates mTOR inhibition and abolishes the resistance of osteosarcoma cells to RAD001 (Everolimus): pivotal role of the prenylation process. , 2010, Cancer research.

[4]  Ji-Youn Han,et al.  Lovastatin overcomes gefitinib resistance in human non-small cell lung cancer cells with K-Ras mutations , 2010, Investigational New Drugs.

[5]  P. Boutros,et al.  Dysregulation of the mevalonate pathway promotes transformation , 2010, Proceedings of the National Academy of Sciences.

[6]  A. Rodrigues.  Efflux and uptake transporters as determinants of statin response , 2010, Expert opinion on drug metabolism & toxicology.

[7]  Sergio A. Rincon,et al.  Rho GTPases: regulation of cell polarity and growth in yeasts. , 2010, The Biochemical journal.

[8]  Chih-Yuan Wang,et al.  In vivo evidence of duality effects for lovastatin in a nude mouse cancer model , 2010, International journal of cancer.

[9]  C. Rao,et al.  Synergistic effects of lovastatin and celecoxib on caveolin-1 and its down-stream signaling molecules: Implications for colon cancer prevention. , 2009, International journal of oncology.

[10]  J. Mehta,et al.  Statins and angiogenesis: is it about connections? , 2009, Biochemical and biophysical research communications.

[11]  V. Steele,et al.  Lack of Efficacy of the Statins Atorvastatin and Lovastatin in Rodent Mammary Carcinogenesis , 2009, Cancer Prevention Research.

[12]  B. Karlan,et al.  Impact of statin therapy on survival in epithelial ovarian cancer. , 2008, Gynecologic oncology.

[13]  M. Caraglia,et al.  Lovastatin induces apoptosis of k-ras-transformed thyroid cells via inhibition of ras farnesylation and by modulating redox state , 2008, Journal of Molecular Medicine.

[14]  D. Heymann,et al.  Liposomal muramyl tripeptide phosphatidyl ethanolamine: a safe and effective agent against osteosarcoma pulmonary metastases , 2008, Expert review of anticancer therapy.

[15]  P. Hulley,et al.  Apomine Enhances the Antitumor Effects of Lovastatin on Myeloma Cells by Down-Regulating 3-Hydroxy-3-methylglutaryl-Coenzyme A Reductase , 2007, Journal of Pharmacology and Experimental Therapeutics.

[16]  P. Croucher,et al.  Apomine™, an inhibitor of HMG‐CoA‐reductase, promotes apoptosis of myeloma cells in vitro and is associated with a modulation of myeloma in vivo , 2007, International journal of cancer.

[17]  Yong Zhou,et al.  Influences of Lovastatin on membrane ion flow and intracellular signaling in breast cancer cells , 2006, Cellular & Molecular Biology Letters.

[18]  S. Sleijfer,et al.  The potential of statins as part of anti-cancer treatment. , 2005, European journal of cancer.

[19]  Henk-Jan Guchelaar,et al.  Effects of statins and farnesyltransferase inhibitors on the development and progression of cancer. , 2004, Cancer treatment reviews.

[20]  Peter L Bonate,et al.  Population pharmacokinetics of APOMINE: a meta-analysis in cancer patients and healthy males. , 2004, British journal of clinical pharmacology.

[21]  C. Ammon-Zufferey,et al.  Apomine, a Novel Hypocholesterolemic Agent, Accelerates Degradation of 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase and Stimulates Low Density Lipoprotein Receptor Activity* , 2004, Journal of Biological Chemistry.

[22]  G. Kruh.  Introduction to resistance to anticancer agents , 2003, Oncogene.

[23]  Tomoyuki Saito,et al.  Inhibition of lung metastasis of osteosarcoma cell line POS-1 transplanted into mice by thigh ligation. , 2002, Cancer letters.

[24]  J. Deisenhofer,et al.  Structural Mechanism for Statin Inhibition of HMG-CoA Reductase , 2001, Science.

[25]  D. Alberts,et al.  Phase I pharmacokinetic trial and correlative in vitro phase II tumor kinetic study of Apomine (SR-45023A), a novel oral biphosphonate anticancer drug. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[26]  E. Niesor,et al.  The nuclear receptors FXR and LXRalpha: potential targets for the development of drugs affecting lipid metabolism and neoplastic diseases. , 2001, Current pharmaceutical design.

[27]  E. Niesor,et al.  The mevalonate/isoprenoid pathway inhibitor apomine (SR-45023A) is antiproliferative and induces apoptosis similar to farnesol. , 2000, Biochemical and biophysical research communications.

[28]  K. Suckling,et al.  Hypocholesterolaemic and Antiatherosclerotic Effects of Tetra-iso-propyl 2-(3,5-Di-tert-butyl-4-hydroxyphenyl)ethyl-1, 1-diphosphonate (SR-9223i) , 2000, Arzneimittelforschung.

[29]  K. Brindle,et al.  Inhibition of Phosphatidylcholine Biosynthesis following Induction of Apoptosis in HL-60 Cells* , 1999, The Journal of Biological Chemistry.

[30]  G. Favre,et al.  Competitive Inhibition of Choline Phosphotransferase by Geranylgeraniol and Farnesol Inhibits Phosphatidylcholine Synthesis and Induces Apoptosis in Human Lung Adenocarcinoma A549 Cells* , 1998, The Journal of Biological Chemistry.

[31]  D. Samid,et al.  Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[32]  P. Edwards,et al.  Identification of farnesol as the non-sterol derivative of mevalonic acid required for the accelerated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. , 1994, The Journal of biological chemistry.

[33]  P. Voziyan,et al.  Farnesol inhibits phosphatidylcholine biosynthesis in cultured cells by decreasing cholinephosphotransferase activity. , 1993, The Biochemical journal.

[34]  S. Sebti,et al.  Lovastatin, a cholesterol biosynthesis inhibitor, inhibits the growth of human H-ras oncogene transformed cells in nude mice. , 1991, Cancer communications.

[35]  R. Evans,et al.  Differential inhibitory effects of lovastatin on protein isoprenylation and sterol synthesis. , 1990, The Journal of biological chemistry.

[36]  M. Nakanishi,et al.  Multivalent control of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Mevalonate-derived product inhibits translation of mRNA and accelerates degradation of enzyme. , 1988, The Journal of biological chemistry.

[37]  R. Defendini,et al.  Suppression of murine neuroblastoma growth in vivo by mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. , 1985, Journal of Clinical Investigation.

[38]  B. Klein,et al.  Studies of bone and soft‐tissue tumours induced in rats with radioactive cerium chloride , 1977, International journal of cancer.

[39]  G. Rosen,et al.  Chemotherapy, en bloc resection, and prosthetic bone replacement in the treatment of osteogenic sarcoma , 1976, Cancer.

[40]  L. Esserman,et al.  Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer , 2009, Breast Cancer Research and Treatment.

[41]  L. Penn,et al.  Differential sensitivity of various pediatric cancers and squamous cell carcinomas to lovastatin-induced apoptosis: therapeutic implications. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.