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Horm Metab Res 2014; 46(07): 471-476
DOI: 10.1055/s-0034-1370991
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

AKT and AMPK Activation after High-Fat and High-Glucose In Vitro Treatment of Prostate Epithelial Cells

D. L. Ribeiro
1   Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia – UFU, Uberlândia, Brazil
,
R. M. Góes
2   Instituto de Biociências, Letras e Ciências Exatas, São Paulo State University – UNESP, São Paulo, Brazil
,
M. E. Pinto-Fochi
2   Instituto de Biociências, Letras e Ciências Exatas, São Paulo State University – UNESP, São Paulo, Brazil
,
S. R. Taboga
2   Instituto de Biociências, Letras e Ciências Exatas, São Paulo State University – UNESP, São Paulo, Brazil
,
P.-A. Abrahamsson
3   Department of Urology, Lund University, Malmö University Hospital, Malmö, Sweden
,
N. Dizeyi
3   Department of Urology, Lund University, Malmö University Hospital, Malmö, Sweden
› Author Affiliations
Further Information

Publication History

received 09 November 2013

accepted 18 February 2014

Publication Date:
05 May 2014 (online)

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Abstract

Considering the increasing consumption of saturated fat and glucose in diets worldwide and its possible association to carcinogenesis, this investigation analysed the proliferation profile of nonmalignant human prostate epithelial cells after exposure to elevated levels of fat and glucose. PNT1A cells were cultured with palmitate (100 or 200 μM) and/or glucose (450 mg/dl) for 24 or 48 h. Treated cells were evaluated for viability test and cell proliferation (MTS assay). AKT and AMPK phosphorylation status were analysed by Western blotting. After 24 h of high-fat alone or associated with high-glucose treatment, there was an increase in AMPK and AKT activation associated to unchanged MTS-cell proliferation. Following 48 h of high-fat but not high-glucose alone, cells decreased AMPK activation and maintained elevated AKT levels. These data were associated to increased cell proliferation after further high-fat treatment. After longer high-fat exposure, MTS revealed that cells remained proliferating. High-glucose alone or associated to high-fat treatment was not able to increase cell proliferation and AKT activation. A high-fat medium containing 100 μM of palmitate stimulates proliferation in PNT1A cells by decreasing the activation of AMPK and increasing activation of AKT after longer exposure time. These findings improve the knowledge about the negative effect of high levels of this saturated fatty acid on proliferative disorders of prostate.

Key words

prostate - palmitate - glucose - cell proliferation - AMPK - AKT
 

  • References

  • 1 Saad F, Gooren LJ. The role of testosterone in the etiology and treatment of obesity, the metabolic syndrome, and diabetes mellitus type 2. J Obes 2011; 471-584
    PubMedGoogle Scholar
  • 2 Howlader N, Noone A, Krapcho M, Garshell J, Neyman N, Altekruse S, Kosary C, Yu M, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Lewis D, Chen H, Feuer E. SEER Cancer Statistics Review, (1975–2010). National Cancer Institute. Available from URL http://seer.cancer.gov/csr/1975_2010/ Accessed 30 January 2014
    PubMedGoogle Scholar
  • 3 Pandian SS, Eremin OE, McClinton S, Wahle KW, Heys SD. Fatty acids and prostate cancer: current status and future challenges. J R Coll Surg Edinb 1999; 44: 352-361
    PubMedGoogle Scholar
  • 4 Crowe FL, Allen NE, Appleby PN, Overvad K, Aardestrup IV, Johnsen NF, Tjonneland A, Linseisen J, Kaaks R, Boeing H, Kroger J, Trichopoulou A, Zavitsanou A. Fatty acid composition of plasma phospholipids and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 2008; 88: 1353-1363
    PubMedGoogle Scholar
  • 5 Pelser C, Mondul AM, Hollenbeck AR, Park Y. Dietary fat, fatty acids, and risk of prostate cancer in the NIH-AARP diet and health study. Cancer Epidemiol Biomarkers Rev 2013; 22: 697-707
    PubMedGoogle Scholar
  • 6 Ribeiro R, Monteiro C, Cunha V, Oliveira MJ, Freitas M, Fraga A, Principe P, Lobato C, Costa C, Cordeiro-da-Silva A, Lopes JM, Lopes C, Medeiros R. Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro. J Exp Clin Cancer Res 2012; 2: 31-32
    PubMedGoogle Scholar
  • 7 Gruzman A, Babai G, Sasson S. Adenosine Monophosphate-Activated Protein Kinase (AMPK) as a New Target for Antidiabetic Drugs: A Review on Metabolic, Pharmacological and Chemical Considerations. Rev Diabet Stud 2009; 6: 13-36
    CrossrefPubMedGoogle Scholar
  • 8 Costa MM, Violato NM, Taboga SR, Goes RM, Bosqueiro JR. Reduction of insulin signaling pathway IRS-1/IRS-2/AKT/mTOR and decrease of epithelial cell proliferation in the prostate of glucocorticoid-treated rats. Int J Exp Pathol 2012; 93: 188-195
    CrossrefPubMedGoogle Scholar
  • 9 Xiang X, Saha AK, Wen R, Ruderman NB, Luo Z. AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms. Biochem Biophys Res Commun 2004; 321: 161-167
    CrossrefPubMedGoogle Scholar
  • 10 Schultze SM, Hemmings BA, Niessen M, Tschopp O. PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis. Expert Rev Mol Med 2012; 11 (14:e1) 1-21
    PubMedGoogle Scholar
  • 11 Ríos M, Foretz M, Viollet B, Prieto A, Fraga M, Costoya JA, Señarís R. AMPK activation by oncogenesis is required to maintain cancer cell proliferation in astrocytic tumors. Cancer Res 2013; 73: 2628-2638
    CrossrefPubMedGoogle Scholar
  • 12 Carling D. The AMP-activated protein kinase cascade – a unifying system for energy control. Trends Biochem Sci 2004; 29: 18-24
    CrossrefPubMedGoogle Scholar
  • 13 Fogarty S, Hardie DG. Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer. Biochim Biophys Acta 2010; 1804: 581-591
    CrossrefPubMedGoogle Scholar
  • 14 Barb D, Neuwirth A, Mantzoros CS, Balk SP. Adiponectin signals in prostate cancer cells through Akt to activate the mammalian target of rapamycin pathway. Endocr Relat Cancer 2007; 14: 995-1005
    CrossrefPubMedGoogle Scholar
  • 15 Park HU, Suy S, Danner M, Dailey V, Zhang Y, Li H, Hyduke DR, Collins BT, Gagnon G, Kallakury B, Kumar D, Brown ML, Fornace A, Dritschilo A, Collins SP. AMP-activated protein kinase promotes human prostate cancer cell growth and survival. Mol Cancer Ther 2009; 8: 733-741
    CrossrefPubMedGoogle Scholar
  • 16 Zadra G, Priolo C, Patnaik A, Loda M. New strategies in prostate cancer: targeting lipogenic pathways and the energy sensor AMPK. Clin Cancer Res 2010; 16: 3322-3328
    CrossrefPubMedGoogle Scholar
  • 17 Escobar EL, Gomes-Marcondes MC, Carvalho HF. Dietary fatty acid quality affects AR and PPARgamma levels and prostate growth. Prostate 2009; 69: 548-558
    CrossrefPubMedGoogle Scholar
  • 18 Ribeiro DL, Pinto ME, Maeda SY, Taboga SR, Goes RM. High fat-induced obesity associated with insulin-resistance increases FGF-2 content and causes stromal hyperplasia in rat ventral prostate. Cell Tis Res 2012; 49: 577-588
    PubMedGoogle Scholar
  • 19 Vikram A, Jena GB, Ramarao P. Increased cell proliferation and contractility of prostate in insulin resistant rats: linking hyperinsulinemia with benign prostate hyperplasia. Prostate 2010; 70: 79-89
    CrossrefPubMedGoogle Scholar
  • 20 Vikram A, Jena G. Diet-induced hyperinsulinemia accelerates growth of androgen-independent PC-3 cells in vitro. Nutr Cancer 2012; 64: 121-127
    CrossrefPubMedGoogle Scholar
  • 21 Bassett JK, Severi G, Hodge AM, Macinnis RJ, Gibson RA, Hopper JL, English DR, Giles GG. Plasma phospholipid fatty acids, dietary fatty acids and prostate cancer risk. Int J Cancer 2013; 133: 1882-1891
    CrossrefPubMedGoogle Scholar
  • 22 Ribeiro DL, Pinto ME, Rafacho A, Bosqueiro JR, Maeda SY, Anselmo-Franci JA, Taboga SR, Goes RM. High-Fat Diet Obesity Associated with Insulin Resistance Increases Cell Proliferation, Estrogen Receptor, and PI3K Proteins in Rat Ventral Prostate. J Androl 2012; 33: 854-865
    CrossrefPubMedGoogle Scholar
  • 23 Jee SH, Ohrr H, Sull JW. Fasting serum glucose level and cancer risk in Korean men and women. JAMA 2005; 293: 194-202
    CrossrefPubMedGoogle Scholar
  • 24 Rapp K, Schroeder J, Klenk J, Ulmer H, Concin H, Diem G, Oberaigner W, Weiland SK. Fasting blood glucose and cancer risk in a cohort of more than 140 000 adults in Austria. Diabetologia 2006; 49: 945-952
    CrossrefPubMedGoogle Scholar
  • 25 Stattin P, Bjor O, Ferrari P, Lukanova A, Lenner P, Lindahl B, Hallmans G, Kaaks R. Prospective study of hyperglycemia and cancer risk. Diabetes Care 2007; 30: 561-567
    CrossrefPubMedGoogle Scholar
  • 26 Stocks T, Rapp K, Bjorge T, Manjer J, Ulmer H, Selmer R, Lukanova A, Johansen D, Concin H, Tretli S, Hallmans G, Jonsson H, Stattin P. Blood glucose and risk of incident and fatal cancer in the metabolic syndrome and cancer project (me-can): analysis of six prospective cohorts. PLoS Med 2009; 6: e1000201
    CrossrefPubMedGoogle Scholar
  • 27 Berquin IM, Edwards IJ, Kridel SJ, Chen YQ. Polyunsaturated fatty acid metabolism in prostate cancer. Cancer Metastasis Rev 2011; 30: 295-309
    CrossrefPubMedGoogle Scholar
  • 28 Cnop M, Hannaert JC, Hoorens A, Eizirik DL, Pipeleers DG. Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation. Diabetes 2001; 50: 1771-1777
    CrossrefPubMedGoogle Scholar
  • 29 Miller TA, LeBrasseur NK, Cote GM, Trucillo MP, Pimentel DR, Ido Y, Ruderman NB, Sawyer DB. Oleate prevents palmitate-induced cytotoxic stress in cardiac myocytes. Biochem Biophys Res Commun 2005; 336: 309-315
    CrossrefPubMedGoogle Scholar
  • 30 Magdalon J, Hatanaka E, Romanatto T, Rodrigues HG, Kuwabara WM, Scaife C, Newsholme P, Curi R. A proteomic analysis of the functional effects of fatty acids in NIH 3T3 fibroblasts. Lipids Health Dis 2011; 24: 210-218
    PubMedGoogle Scholar
  • 31 Chung JH, Jeon HJ, Hong SY, Lee L, Lee KH, Kim SH, Manabe I, Miller YI, Lee SH. Palmitate promotes the paracrine effects of macrophages on vascular smooth muscle cells: the role of bone morphogenetic proteins. PLoS One 2012; 7: e29100
    CrossrefPubMedGoogle Scholar
  • 32 Sun M, Paciga JE, Feldman RI, Yuan Z, Coppola D, Lu YY, Shelley SA, Nicosia SV, Cheng JQ. Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K. Cancer Res 2001; 61: 5985-5991
    PubMedGoogle Scholar
  • 33 Zeng L, Biernacka KM, Holly JM, Jarrett C, Morrison AA, Morgan A, Morgan A, Winters ZE, Foulstone EJ, Shield JP, Perks CM. Hyperglycaemia confers resistance to chemotherapy on breast cancer cells: the role of fatty acid synthase. Endocr Relat Cancer 2010; 17: 539-551
    CrossrefPubMedGoogle Scholar
  • 34 Kim JM, Song PH, Kim HT, Moon KH. Effect of obesity on prostate-specific antigen, prostate volume, and international prostate symptom score in patients with benign prostatic hyperplasia. Korean J Urol 2011; 52: 401-405
    CrossrefPubMedGoogle Scholar
  • 35 Bonorden MJ, Grossmann ME, Ewing SA, Rogozina OP, Ray A, Nkhata KJ, Liao DJ, Grande JP, Cleary MP. Growth and Progression of TRAMP Prostate Tumors in Relationship to Diet and Obesity. Prostate Cancer 2012; 543-570
    PubMedGoogle Scholar
  • 36 Sarker D, Reid AH, Yap TA, de Bono JS. Targeting the PI3K/AKT pathway for the treatment of prostate cancer. Clin Cancer Res 2009; 15: 4799-4805
    CrossrefPubMedGoogle Scholar
  • 37 Schultze SM, Hemmings BA, Niessen M, Tschopp O. PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis. Expert Rev Mol Med 2012; 11 (14:e1) 1-21
    PubMedGoogle Scholar
  • 38 Carling D. The AMP-activated protein kinase cascade – a unifying system for energy control. Trends Biochem Sci 2004; 29: 18-24
    CrossrefPubMedGoogle Scholar
  • 39 Bolster DR, Crozier SJ, Kimball SR, Jefferson LS. AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem 2002; 277: 23977-23980
    CrossrefPubMedGoogle Scholar
  • 40 Kimura N, Tokunaga C, Dalal S, Richardson C, Yoshino K, Hara K, Kemp BE, Witters LA, Mimura O, Yonezawa K. A Possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway. Genes Cells 2003; 8: 65-79
    CrossrefPubMedGoogle Scholar