Anti-Tumorigenic Potential of a Novel Orlistat-AICAR Combination in Prostate Cancer Cells

Journal of Cellular Biochemistry

Volumn 118, Issue 11, 2017, Pages 3834-3845

  Wright, Clayton ^a   Iyer, Anand Krishnan V ^a   Kaushik, Vivek ^a   Azad, Neelam ^a  

^a HAMPTON UNIVERSITY   (United States)

Author keywords

AICAR; AMPK; FATTY ACID SYNTHASE; ORLISTAT; PROSTATE CANCER (PCa)

Indexed keywords

5 AMINO 4 IMIDAZOLECARBOXAMIDE RIBOSIDE; CASPASE 3; CASPASE 8; CASPASE 9; FATTY ACID SYNTHASE; REACTIVE OXYGEN METABOLITE; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; TETRAHYDROLIPSTATIN; VASCULOTROPIN; 5 AMINO 4 IMIDAZOLECARBOXAMIDE; AICA RIBONUCLEOTIDE; LACTONE; RIBONUCLEOTIDE; TUMOR PROTEIN;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; DOWN REGULATION; DRUG MECHANISM; DRUG POTENTIATION; ENZYME ACTIVATION; G1 PHASE CELL CYCLE CHECKPOINT; IN VITRO STUDY; MIGRATION INHIBITION; PRIORITY JOURNAL; PROSTATE CANCER; PROSTATE CANCER CELL LINE; PROTEIN EXPRESSION; ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS; CELL CYCLE G0 PHASE; CELL MOTION; DRUG EFFECTS; HUMAN; MALE; METABOLISM; PATHOLOGY; PROSTATE TUMOR; TUMOR CELL LINE;

AMINOIMIDAZOLE CARBOXAMIDE; APOPTOSIS; CELL LINE, TUMOR; CELL MOVEMENT; G1 PHASE CELL CYCLE CHECKPOINTS; HUMANS; LACTONES; MALE; NEOPLASM PROTEINS; PROSTATIC NEOPLASMS; REACTIVE OXYGEN SPECIES; RESTING PHASE, CELL CYCLE; RIBONUCLEOTIDES;

EID: 85019595093     PISSN: 07302312     EISSN: 10974644     Source Type: Journal    
DOI: 10.1002/jcb.26033     Document Type: Article

References (56)

1. Bliss CI. 1939. The toxicity of poisons applied jointly. Ann Appl Biol 26:585–615.
2. Carlsson S, Vickers AJ, Roobol M, Eastham J, Scardino P, Lilja H, Hugosson J. 2012. Prostate cancer screening: Facts, statistics, and interpretation in response to the US preventive services task force review. J Clin Oncol 30:2581–2584.
3. Carvalho MA, Zecchin KG, Seguin F, Bastos DC, Agostini M, Rangel AL, Veiga SS, Raposo HF, Oliveira HC, Loda M, Coletta RD, Graner E. 2008. Fatty acid synthase inhibition with Orlistat promotes apoptosis and reduces cell growth and lymph node metastasis in a mouse melanoma model. Int J Cancer 123:2557–2565.
4. Davidson MH, Hauptman J, DiGirolamo M, Foreyt JP, Halsted CH, Heber D, Heimburger DC, Lucas CP, Robbins DC, Chung J, Heymsfield SB. 1999. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: A randomized controlled trial. JAMA 281:235–242.
5. Diaz-Moralli S, Tarrado-Castellarnau M, Miranda A, Cascante M. 2013. Targeting cell cycle regulation in cancer therapy. Pharmacol Ther 138:255–271.
6. Ettinger SL, Sobel R, Whitmore TG, Akbari M, Bradley DR, Gleave ME, Nelson CC. 2004. Dysregulation of sterol response element-binding proteins and downstream effectors in prostate cancer during progression to androgen independence. Cancer Res 64:2212–2221.
7. Ferrara N, Houck K, Jakeman L, Leung DW. 1992. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 13:18–32.
8. Field FJ, Born E, Murthy S, Mathur SN. 2002. Polyunsaturated fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 cells: Effect on fatty acid synthesis and triacylglycerol transport. Biochem J 368:855–864.
9. Folkman J. 1993. Diagnostic and therapeutic applications of angiogenesis research. C R Acad Sci III 316:909–918.
10. Ford OH, 3rd, Gregory CW, Kim D, Smitherman AB, Mohler JL. 2003. Androgen receptor gene amplification and protein expression in recurrent prostate cancer. J Urol 170:1817–1821.
11. Fujiwara J, Sowa Y, Horinaka M, Koyama M, Wakada M, Miki T, Sakai T. 2012. The anti-obesity drug orlistat promotes sensitivity to TRAIL by two different pathways in hormone-refractory prostate cancer cells. Int J Oncol 40:1483–1491.
12. Furuta E, Pai SK, Zhan R, Bandyopadhyay S, Watabe M, Mo YY, Hirota S, Hosobe S, Tsukada T, Miura K, Kamada S, Saito K, Iiizumi M, Liu W, Ericsson J, Watabe K. 2008. Fatty acid synthase gene is up-regulated by hypoxia via activation of Akt and sterol regulatory element binding protein-1. Cancer Res 68:1003–1011.
13. Furuya Y, Akimoto S, Yasuda K, Ito H. 1997. Apoptosis of androgen-independent prostate cell line induced by inhibition of fatty acid synthesis. Anticancer Res 17:4589–4593.
14. Gabrielson EW, Pinn ML, Testa JR, Kuhajda FP. 2001. Increased fatty acid synthase is a therapeutic target in mesothelioma. Clin Cancer Res 7:153–157.
15. Galinanes M, Mullane KM, Bullough D, Hearse DJ. 1992. Acadesine and myocardial protection. Studies of time of administration and dose-response relations in the rat. Circulation 86:598–608.
16. Gartel AL, Radhakrishnan SK. 2005. Lost in transcription: P21 repression, mechanisms, and consequences. Cancer Res 65:3980–3985.
17. Giro-Perafita A, Palomeras S, Lum DH, Blancafort A, Vinas G, Oliveras G, Perez-Bueno F, Sarrats A, Welm AL, Puig T. 2016. Preclinical evaluation of fatty acid synthase and EGFR inhibition in triple-negative beast cancer. Clin Cancer Res 18:4687–4697.
18. Goldfarb M. 1990. The fibroblast growth factor family. Cell Growth Differ 1:439–445.
19. Grivas N, Goussia A, Stefanou D, Giannakis D. 2016. Microvascular density and immunohistochemical expression of VEGF, VEGFR-1 and VEGFR-2 in benign prostatic hyperplasia, high-grade prostate intraepithelial neoplasia and prostate cancer. Cent European J Urol 69:63–71.
20. Hardie DG. 2004. The AMP-activated protein kinase pathway-new players upstream and downstream. J Cell Sci 117:5479–5487.
21. He L, Zhou X, Huang N, Li H, Tian J, Li T, Yao K, Wu G, Nyachoti CM, Kim SW, Yin Y. 2016. The mechanism of AMPK regulation on glucose, lipid and protein metabolic homeostasis and its related physiologically nutritional significance. Curr Protein Pept Sci 18:562–570.
22. Heiligtag SJ, Bredehorst R, David KA. 2002. Key role of mitochondria in cerulenin-mediated apoptosis. Cell Death Differ 9:1017–1025.
23. Jayakumar A, Tai MH, Huang WY, al-Feel W, Hsu M, Abu-Elheiga L, Chirala SS, Wakil SJ. 1995. Human fatty acid synthase: Properties and molecular cloning. Proc Natl Acad Sci USA 92:8695–8699.
24. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. 2011. Global cancer statistics. CA Cancer J Clin 61:69–90.
25. Kemmerer M, Finkernagel F, Cavalcante MF, Abdalla DS, Muller R, Brune B, Namgaladze D. 2015. AMP-Activated protein kinase interacts with the peroxisome proliferator-activated receptor delta to induce genes affecting fatty acid oxidation in human macrophages. PLoS ONE 10:e0130893.
26. Kim WH, Lee JW, Suh YH, Lee HJ, Lee SH, Oh YK, Gao B, Jung MH. 2007. AICAR potentiates ROS production induced by chronic high glucose: Roles of AMPK in pancreatic beta-cell apoptosis. Cell Signal 19:791–805.
27. Knudsen KE, Scher HI. 2009. Starving the addiction: New opportunities for durable suppression of AR signaling in prostate cancer. Clin Cancer Res 15:4792–4798.
28. Kurahashi N, Inoue M, Iwasaki M, Sasazuki S, Tsugane AS. 2008. Dairy product, saturated fatty acid, and calcium intake and prostate cancer in a prospective cohort of Japanese men. Cancer Epidemiol Biomarkers Prev 17:930–937.
29. Linja MJ, Savinainen KJ, Saramaki OR, Tammela TL, Vessella RL, Visakorpi T. 2001. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res 61:3550–3555.
30. Mavrou A, Oltean S. 2016. SRPK1 inhibition in prostate cancer: A novel anti-angiogenic treatment through modulation of VEGF alternative splicing. Pharmacol Res 107:276–281.
31. Menendez JA, Lupu R. 2007. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 7:763–777.
32. Menendez JA, Vellon L, Lupu R. 2005. Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: Blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene. Ann Oncol 16:1253–1267.
33. Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, Munday NA, Raju SM, Smulson ME, Yamin T, Yu VL, Miller DK. 1995. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376:37–43.
34. Oliver FJ, de la Rubia G, Rolli V, Ruiz-Ruiz MC, de Murcia G, Murcia JM. 1998. Importance of poly(ADP-ribose) polymerase and its cleavage in apoptosis. Lesson from an uncleavable mutant. J Biol Chem 273:33533–33539.
35. Osada S, Naganawa A, Misonou M, Tsuchiya S, Tamba S, Okuno Y, Nishikawa J, Satoh K, Imagawa M, Tsujimoto G, Sugimoto Y, Nishihara T. 2006. Altered gene expression of transcriptional regulatory factors in tumor marker-positive cells during chemically induced hepatocarcinogenesis. Toxicol Lett 167:106–113.
36. Pizer ES, Chrest FJ, DiGiuseppe JA, Han WF. 1998. Pharmacological inhibitors of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines. Cancer Res 58:4611–4615.
37. Pizer ES, Thupari J, Han WF, Pinn ML, Chrest FJ, Frehywot GL, Townsend CA, Kuhajda FP. 2000. Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. Cancer Res 60:213–218.
38. Reed BD, Charos AE, Szekely AM, Weissman SM, Snyder M. 2008. Genome-wide occupancy of SREBP1 and its partners NFY and SP1 reveals novel functional roles and combinatorial regulation of distinct classes of genes. PLoS Genet 4:e1000133.
39. Rodriguez R, Meuth M. 2006. Chk1 and p21 cooperate to prevent apoptosis during DNA replication fork stress. Mol Biol Cell 17:402–412.
40. Sadowski MC, Pouwer RH, Gunter JH, Lubik AA, Quinn RJ, Nelson CC. 2014. The fatty acid synthase inhibitor triclosan: Repurposing an anti-microbial agent for targeting prostate cancer. Oncotarget 5:9362–9381.
41. Sauer H, Engel S, Milosevic N, Sharifpanah F, Wartenberg M. 2012. Activation of AMP-kinase by AICAR induces apoptosis of DU-145 prostate cancer cells through generation of reactive oxygen species and activation of c-Jun N-terminal kinase. Int J Oncol 40:501–508.
42. Siegel RL, Miller KD, Jemal A. 2015. Cancer statistics, 2015. CA Cancer J Clin 65:5–29.
43. Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ. 1999. Ordering the cytochrome c-initiated caspase cascade: Hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol 144:281–292.
44. Smith S, Witkowski A, Joshi AK. 2003. Structural and functional organization of the animal fatty acid synthase. Prog Lipid Res 42:289–317.
45. Sullivan JE, Brocklehurst KJ, Marley AE, Carey F, Carling D, Beri RK. 1994. Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell-permeable activator of AMP-activated protein kinase. FEBS Lett 353:33–36.
46. Swinnen JV, Van Veldhoven PP, Timmermans L, De Schrijver E, Brusselmans K, Vanderhoydonc F, Van de Sande T, Heemers H, Heyns W, Verhoeven G. 2003. Fatty acid synthase drives the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains. Biochem Biophys Res Commun 302:898–903.
47. Thupari JN, Kim EK, Moran TH, Ronnett GV, Kuhajda FP. 2004. Chronic C75 treatment of diet-induced obese mice increases fat oxidation and reduces food intake to reduce adipose mass. Am J Physiol Endocrinol Metab 287:E97–E104.
48. Tong L. 2005. Acetyl-coenzyme A carboxylase: Crucial metabolic enzyme and attractive target for drug discovery. Cell Mol Life Sci 62:1784–1803.
49. Venkatadri R, Muni T, Iyer AK, Yakisich JS, Azad N. 2016. Role of apoptosis-related miRNAs in resveratrol-induced breast cancer cell death. Cell Death Dis 7:e2104.
50. Viollet B, Horman S, Leclerc J, Lantier L, Foretz M, Billaud M, Giri S, Andreelli F. 2010. AMPK inhibition in health and disease. Crit Rev Biochem Mol Biol 45:276–295.
51. Wakil SJ. 1989. Fatty acid synthase, a proficient multifunctional enzyme. Biochemistry 28:4523–4530.
52. Yoshii Y, Furukawa T, Oyama N, Hasegawa Y, Kiyono Y, Nishii R, Waki A, Tsuji AB, Sogawa C, Wakizaka H, Fukumura T, Yoshii H, Fujibayashi Y, Lewis JS, Saga T. 2013. Fatty acid synthase is a key target in multiple essential tumor functions of prostate cancer: Uptake of radiolabeled acetate as a predictor of the targeted therapy outcome. PLoS ONE 8:e64570.
53. Zecchin KG, Rossato FA, Raposo HF, Melo DR, Alberici LC, Oliveira HC, Castilho RF, Coletta RD, Vercesi AE, Graner E. 2011. Inhibition of fatty acid synthase in melanoma cells activates the intrinsic pathway of apoptosis. Lab Invest 91:232–240.
54. Zhang BB, Zhou G, Li C. 2009. AMPK: An emerging drug target for diabetes and the metabolic syndrome. Cell Metab 9:407–416.
55. Zhao W, Sachsenmeier K, Zhang L, Sult E, Hollingsworth RE, Yang H. 2014. A new bliss independence model to analyze drug combination data. J Biomol Screen 19:817–821.
56. Zhi J, Melia AT, Eggers H, Joly R, Patel IH. 1995. Review of limited systemic absorption of orlistat, a lipase inhibitor, in healthy human volunteers. J Clin Pharmacol 35:1103–1108.