Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis

Biochemical Journal

Volumn 469, Issue 2, 2015, Pages 177-187

  O'Brien, Andrew J ^a   Villani, Linda A ^a   Broadfield, Lindsay A ^a   Houde, Vanessa P ^a   Galic, Sandra ^b   Blandino, Giovanni ^a,c   Kemp, Bruce E ^b   Tsakiridis, Theodoros ^a   Muti, Paola ^a   Steinberg, Gregory R ^a  

^a MCMASTER UNIVERSITY   (Canada)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c REGINA ELENA NATIONAL CANCER INSTITUTE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYL COENZYME A CARBOXYLASE; CHOLESTEROL; FATTY ACID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; METFORMIN; SALICYLIC ACID; ANTIDIABETIC AGENT; NONSTEROID ANTIINFLAMMATORY AGENT; SALICYLATE SODIUM; TUMOR PROTEIN;

ANIMAL CELL; ARTICLE; CANCER CELL; CELL PROLIFERATION; CELL SURVIVAL; CONTROLLED STUDY; DRUG POTENTIATION; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; EX VIVO STUDY; FATTY ACID SYNTHESIS; FIBROBLAST; LIPOGENESIS; LUNG CANCER; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; AGONISTS; ANIMAL; ANIMAL EMBRYO; BINDING SITE; DRUG EFFECTS; ENZYMOLOGY; FEMALE; GENETICS; HUMAN; KNOCKOUT MOUSE; LUNG NEOPLASMS; MALE; METABOLISM; PATHOLOGY; PROSTATIC NEOPLASMS; TUMOR CELL LINE;

ACETYL-COA CARBOXYLASE; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; BINDING SITES; CELL LINE, TUMOR; CELL SURVIVAL; DRUG SYNERGISM; EMBRYO, MAMMALIAN; ENZYME ACTIVATION; FEMALE; FIBROBLASTS; HUMANS; HYPOGLYCEMIC AGENTS; LIPOGENESIS; LUNG NEOPLASMS; MALE; METFORMIN; MICE; MICE, KNOCKOUT; NEOPLASM PROTEINS; PROSTATIC NEOPLASMS; SODIUM SALICYLATE;

EID: 84937134138     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20150122     Document Type: Article

References (57)

1. Rothwell, P.M., Fowkes, F.G.R., Belch, J.F., Ogawa, H., Warlow, C.P. and Meade, T.W. (2011) Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 377, 31-41 CrossRef PubMed
2. Liu, Y., Chen, J.Q., Xie, L., Wang, J., Li, T., He, Y., Gao, Y., Qin, X. and Li, S. (2014) Effect of aspirin and other non-steroidal anti-inflammatory drugs on prostate cancer incidence and mortality: a systematic review and meta-analysis. BMC Med. 12, 55 CrossRef PubMed
3. Shebl, F.M., Sakoda, L.C., Black, A., Koshiol, J., Andriole, G.L., Grubb, R., Church, T.R., Chia, D., Zhou, C., Chu, L.W. et al. (2012) Aspirin but not ibuprofen use is associated with reduced risk of prostate cancer: a PLCO study. Br. J. Cancer 107, 207-214 CrossRef PubMed
4. Thun, M.J., Namboodiri, M.M., Calle, E.E., Flanders, W.D. and Heath, C.W. (1993) Aspirin use and risk of fatal cancer. Cancer Res. 53, 1322-1327 PubMed
5. Din, F.V., Theodoratou, E., Farrington, S.M., Tenesa, A., Barnetson, R.A., Cetnarskyj, R., Stark, L., Porteous, M.E., Campbell, H. and Dunlop, M.G. (2010) Effect of aspirin and NSAIDs on risk and survival from colorectal cancer. Gut 59, 1670-1679 CrossRef PubMed
6. Higgs, G.A., Salmon, J.A., Henderson, B. and Vane, J.R. (1987) Pharmacokinetics of aspirin and salicylate in relation to inhibition of arachidonate cyclooxygenase and antiinflammatory activity. Proc. Natl. Acad. Sci. U.S.A. 84, 1417-1420 CrossRef PubMed
7. Steinberg, G.R., Dandapani, M. and Hardie, D.G. (2013) AMPK: mediating the metabolic effects of salicylate-based drugs? Trends Endocrinol. Metab. 24, 481-487 CrossRef PubMed
8. Hawley, S.A., Fullerton, M.D., Ross, F.A., Schertzer, J.D., Chevtzoff, C., Walker, K.J., Peggie, M.W., Zibrova, D., Green, K.A., Mustard, K.J. et al. (2012) The ancient drug salicylate directly activates AMP-activated protein kinase. Science 336, 918-922 CrossRef PubMed
9. Hay, N. (2005) The Akt-mTOR tango and its relevance to cancer. Cancer Cell 8, 179-183 CrossRef PubMed
10. Gwinn, D.M., Shackelford, D.B., Egan, D.F., Mihaylova, M.M., Mery, A., Vasquez, D.S., Turk, B.E. and Shaw, R.J. (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol. Cell 30, 214-226 CrossRef PubMed
11. Inoki, K., Zhu, T. and Guan, K.L. (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115, 577-590 CrossRef PubMed
12. Manning, B.D. and Cantley, L.C. (2003) United at last: the tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signalling. Biochem. Soc. Trans. 31, 573-578 CrossRef PubMed
13. Law, B.K., Waltner-Law, M.E., Entingh, A.J., Chytil, A., Aakre, M.E., Norgaard, P. and Moses, H.L. (2000) Salicylate-induced growth arrest is associated with inhibition of p70s6k and down-regulation of c-myc, cyclin D1, cyclin A, and proliferating cell nuclear antigen. J. Biol. Chem. 275, 38261-38267 CrossRef PubMed
14. Lissa, D., Senovilla, L., Rello-Varona, S., Vitale, I., Michaud, M., Pietrocola, F., Boileve, A., Obrist, F., Bordenave, C., Garcia, P. et al. (2014) Resveratrol and aspirin eliminate tetraploid cells for anticancer chemoprevention. Proc. Natl. Acad. Sci. U.S.A. 111, 3020-3025 CrossRef PubMed
15. Din, F.V., Valanciute, A., Houde, V.P., Zibrova, D., Green, K.A., Sakamoto, K., Alessi, D.R. and Dunlop, M.G. (2012) Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells. Gastroenterology 142, 1504-1515 e1503 CrossRef
16. Vincent, E.E., Coelho, P.P., Blagih, J., Griss, T., Viollet, B. and Jones, R.G. (2014) Differential effects of AMPK agonists on cell growth and metabolism. Oncogene, doi: 10.1038/onc.2014.301
17. Blandino, G., Valerio, M., Cioce, M., Mori, F., Casadei, L., Pulito, C., Sacconi, A., Biagioni, F., Cortese, G., Galanti, S. et al. (2012) Metformin elicits anticancer effects through the sequential modulation of DICER and c-MYC. Nat. Commun. 3, 865 CrossRef PubMed
18. Barba, M. and Muti, P. (2009) Is it time to test metformin in breast cancer prevention trials? A reply to the authors. Cancer Epidemiol. Biomarkers Prev. 18, 2565 CrossRef PubMed
19. Muti, P., Berrino, F., Krogh, V., Villarini, A., Barba, M., Strano, S. and Blandino, G. (2009) Metformin, diet and breast cancer: an avenue for chemoprevention. Cell Cycle 8, 2661 CrossRef PubMed
20. Barba, M., Schunemann, H.J., Sperati, F., Akl, E.A., Musicco, F., Guyatt, G. and Muti, P. (2009) The effects of metformin on endogenous androgens and SHBG in women: a systematic review and meta-analysis. Clin. Endocrinol. 70, 661-670 CrossRef
21. Anisimov, V.N., Berstein, L.M., Egormin, P.A., Piskunova, T.S., Popovich, I.G., Zabezhinski, M.A., Kovalenko, I.G., Poroshina, T.E., Semenchenko, A.V., Provinciali, M. et al. (2005) Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Exp. Gerontol. 40, 685-693 CrossRef PubMed
22. Dowling, R.J., Goodwin, P.J. and Stambolic, V. (2011) Understanding the benefit of metformin use in cancer treatment. BMC Med. 9, 33 CrossRef PubMed
23. Evans, J.M., Donnelly, L.A., Emslie-Smith, A.M., Alessi, D.R. and Morris, A.D. (2005) Metformin and reduced risk of cancer in diabetic patients. BMJ 330, 1304-1305 CrossRef PubMed
24. Pollak, M. (2010) Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev. Res. 3, 1060-1065 CrossRef
25. Pollak, M. (2013) Potential applications for biguanides in oncology. J. Clin. Invest. 123, 3693-3700 CrossRef PubMed
26. Wheaton, W.W., Weinberg, S.E., Hamanaka, R.B., Soberanes, S., Sullivan, L.B., Anso, E., Glasauer, A., Dufour, E., Mutlu, G.M., Budigner, G.S. and Chandel, N.S. (2014) Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. eLife 3, e02242 CrossRef PubMed
27. Hawley, S.A., Gadalla, A.E., Olsen, G.S. and Hardie, D.G. (2002) The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes 51, 2420-2425 CrossRef PubMed
28. Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N. et al. (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167-1174 CrossRef PubMed
29. Menendez, J.A. and Lupu, R. (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat. Rev. Cancer 7, 763-777 CrossRef PubMed
30. Hardie, D.G. (2008) AMPK: a key regulator of energy balance in the single cell and the whole organism. Int. J. Obesity 32 Suppl 4, S7-S12 CrossRef
31. O'Neill, H.M., Holloway, G.P. and Steinberg, G.R. (2013) AMPK regulation of fatty acid metabolism and mitochondrial biogenesis: implications for obesity. Mol. Cell. Endocrinol. 366, 135-151 CrossRef PubMed
32. Fullerton, M.D., Galic, S., Marcinko, K., Sikkema, S., Pulinilkunnil, T., Chen, Z.P., O'Neill, H.M., Ford, R.J., Palanivel, R., O'Brien, M. et al. (2013) Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat. Med. 19, 1649-1654 CrossRef PubMed
33. Smith, M.J. (1959) The effects of salicylate on the metabolism of acetate in the rat. J. Biol. Chem. 234, 144-147 PubMed
34. Zhou, J., Huang, W., Tao, R., Ibaragi, S., Lan, F., Ido, Y., Wu, X., Alekseyev, Y.O., Lenburg, M.E., Hu, G.F. and Luo, Z. (2009) Inactivation of AMPK alters gene expression and promotes growth of prostate cancer cells. Oncogene 28, 1993-2002 CrossRef PubMed
35. Zadra, G., Photopoulos, C., Tyekucheva, S., Heidari, P., Weng, Q.P., Fedele, G., Liu, H., Scaglia, N., Priolo, C. and Sicinska, E. (2014) A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis. EMBO Mol. Med. 6, 519-538 CrossRef PubMed
36. Xiang, X., Saha, A.K., Wen, R., Ruderman, N.B. and Luo, Z. (2004) AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms. Biochem. Biophys. Res. Commun. 321, 161-167 CrossRef PubMed
37. Sanli, T., Rashid, A., Liu, C., Harding, S., Bristow, R.G., Cutz, J.C., Singh, G., Wright, J. and Tsakiridis, T. (2010) Ionizing radiation activates AMP-activated kinase (AMPK): a target for radiosensitization of human cancer cells. Int. J. Radiat. Oncol. Biol. Phys. 78, 221-229 CrossRef PubMed
38. Chou, T.C., Motzer, R.J., Tong, Y. and Bosl, G.J. (1994) Computerized quantitation of synergism and antagonism of taxol, topotecan, and cisplatin against human teratocarcinoma cell growth: a rational approach to clinical protocol design. J. Natl. Cancer Inst. 86, 1517-1524 CrossRef PubMed
39. Yin, M.-J., Yamamoto, Y. and Gaynor, R.B. (1998) The anti-inflammatory agents aspirin and salicylate inhibit the activity of IκB kinase-β. Nature 396, 77-80 CrossRef PubMed
40. Blacklock, C., Lawrence, J., Wiles, D., Malcolm, E., Gibson, I., Kelly, C. and Paterson, J. (2001) Salicylic acid in the serum of subjects not taking aspirin. Comparison of salicylic acid concentrations in the serum of vegetarians, non-vegetarians, and patients taking low dose aspirin. J. Clin. Pathol. 54, 553-555 CrossRef PubMed
41. Gowans, G.J., Hawley, S.A., Ross, F.A. and Hardie, D.G. (2013) AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab. 18, 556-566 CrossRef PubMed
42. Xiang, X., Saha, A.K., Wen, R., Ruderman, N.B. and Luo, Z. (2004) AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms. Biochem. Biophys. Res. Commun. 321, 161-167 CrossRef PubMed
43. Choudhury, Y., Yang, Z., Ahmad, I., Nixon, C., Salt, I.P. and Leung, H.Y. (2014) AMP-activated protein kinase (AMPK) as a potential therapeutic target independent of PI3K/Akt signaling in prostate cancer. Oncoscience 1, 446-456 PubMed
44. Beynen, A.C. and Geelen, M.J. (1982) Short-term inhibition of fatty acid biosynthesis in isolated hepatocytes by mono-aromatic compounds. Toxicology 24, 183-197 CrossRef PubMed
45. Hundal, R.S., Petersen, K.F., Mayerson, A.B., Randhawa, P.S., Inzucchi, S., Shoelson, S.E. and Shulman, G.I. (2002) Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. J. Clin. Invest. 109, 1321-1326 CrossRef PubMed
46. Algra, A.M. and Rothwell, P.M. (2012) Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol. 13, 518-527 CrossRef PubMed
47. Pizer, E.S., Pflug, B.R., Bova, G.S., Han, W.F., Udan, M.S. and Nelson, J.B. (2001) Increased fatty acid synthase as a therapeutic target in androgen-independent prostate cancer progression. Prostate 47, 102-110 CrossRef PubMed
48. Swinnen, J.V., Esquenet, M., Goossens, K., Heyns, W. and Verhoeven, G. (1997) Androgens stimulate fatty acid synthase in the human prostate cancer cell line LNCaP. Cancer Res. 57, 1086-1090 PubMed
49. Piyathilake, C.J., Frost, A.R., Manne, U., Bell, W.C., Weiss, H., Heimburger, D.C. and Grizzle, W.E. (2000) The expression of fatty acid synthase (FASE) is an early event in the development and progression of squamous cell carcinoma of the lung. Hum. Pathol. 31, 1068-1073 CrossRef PubMed
50. Visca, P., Sebastiani, V., Botti, C., Diodoro, M.G., Lasagni, R.P., Romagnoli, F., Brenna, A., De Joannon, B.C., Donnorso, R.P., Lombardi, G. and Alo, P.L. (2004) Fatty acid synthase (FAS) is a marker of increased risk of recurrence in lung carcinoma. Anticancer Res. 24, 4169-4173 PubMed
51. Edmond, J. and Popjak, G. (1974) Transfer of carbon atoms from mevalonate to n-fatty acids. J. Biol. Chem. 249, 66-71 PubMed
52. Fogelman, A., Edmond, J. and Popjåk, G. (1975) Metabolism of mevalonate in rats and man not leading to sterols. J. Biol. Chem. 250, 1771-1775 PubMed
53. 10) and acylglycerols. Biochim. Biophys. Acta 960, 139-147 CrossRef PubMed
54. El-Mir, M.Y., Nogueira, V., Fontaine, E., Averet, N., Rigoulet, M. and Leverve, X. (2000) Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J. Biol. Chem. 275, 223-228 CrossRef PubMed
55. Ford, R.J., Fullerton, M.D., Pinkosky, S.L., Day, E.A., Scott, J.W., Oakhill, J.S., Bujak, A.L., Smith, B.K., Crane, J.D., Blupsilonmer, R.M. et al. (2015) Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity. Biochem. J. 468, 125-132 CrossRef PubMed
56. Scott, J.W., Ling, N., Issa, S.M., Dite, T.A., O'Brien, M.T., Chen, Z.P., Galic, S., Langendorf, C.G., Steinberg, G.R., Kemp, B.E. and Oakhill, J.S. (2014) Small molecule drug A-769662 and AMP synergistically activate naive AMPK independent of upstream kinase signaling. Chem. Biol. 21, 619-627 CrossRef PubMed
57. Ducommun, S., Ford, R.J., Bultot, L., Deak, M., Bertrand, L., Kemp, B.E., Steinberg, G.R. and Sakamoto, K. (2014) Enhanced activation of cellular AMPK by dual-small molecule treatment: AICAR and A769662. Am. J. Physiol. Endocrinol. Metab. 306, E688-E696 CrossRef PubMed