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Synergic effect of α-tocopherol and naringenin in transglutaminase-induced differentiation of human prostate cancer cells

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Abstract

Prostate cancer is the second most common cancer in men worldwide. Its prevention and treatment remain a challenge to clinicians. Thus, there is an urgent need to discover novel, less toxic, and more effective therapies for patients. Many vitamins and related chemicals, including vitamin E, (tocopherols) have shown their anti-cancer activities as anti-oxidants, activators of transcription factors or factors influencing epigenetic events. Although laboratory tests including the use of animal models showed that this vitamin may have anticancer properties, whether it can effectively prevent the development and/or progression of prostate cancer in humans remains to be intensively studied. This review provides up-to-date information regarding the recent outcomes of laboratory, epidemiology and/or clinical trials on the effects of tocopherols on prostate cancer development, along with our last observations on a combined treatment of a prostate cancer cell line (PC-3) with two natural antineoplastic compounds, naringenin (NG) and α-tocopherol (α-TOC). We report the synergic effect of α-TOC and NG in transglutaminase-induced differentiation of human PC-3 prostate cancer cells. While our results are based on one histological class of tumor, the most significant implication of this observation is that establishes a new way in the screening for detecting new differentiative antineoplastic agents.

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References

  • Ablin RJ, Whyard TC (1991) Identification and biological relevance of spermatozoal transglutaminase. Experientia 47:277–279

    Article  PubMed  CAS  Google Scholar 

  • Adlercreutz H (2002) Phyto-oestrogens and cancer. Lancet Oncol 3(6):364–373

    Article  PubMed  Google Scholar 

  • Ahlbom A, Lichtenstein P, Malmström H, Feychting M, Hemminki K, Pedersen NL (1997) Cancer in twins: genetic and nongenetic familial risk factors. J Natl Cancer Inst 89(4):287–293

    Article  PubMed  CAS  Google Scholar 

  • An G, Meka CS, Bright S, Veltri RW (1999) Human prostate-specific transglutaminase gene: promoter cloning, tissue-specific expression, and down-regulation in metastatic prostate cancer. Urology 54:1105–1111

    Article  PubMed  CAS  Google Scholar 

  • Ablin RJ, Bartkus JM, Gonder MJ, Polgar J (1987) In: Cimino F, Birkmayer CD, Pimental E, Klavins JV, Salvatore F (eds) Factors contributing to suppression of tumor–host responsiveness. Human tumor markers–biology and clinical applications. Walter de Gruyter, Berlin, pp 279–299

  • Beninati S, Abbruzzese A, Cardinali M (1993) Differences in the post-translational modification of proteins by polyamines between weakly and highly metastatic B16 melanoma cells. Int J Cancer 53:792–797

    Article  PubMed  CAS  Google Scholar 

  • Bhat R (1986) Serum, retinal, choroidal vitreal vitamin E concentrations in human infants. Pediatrics 78:866–870

    PubMed  CAS  Google Scholar 

  • Birt DF (1986) Update on the effects of vitamins A, C, and F and selenium on carcinogenesis. Proc Soc Exp Biol Med 183:311–320

    PubMed  CAS  Google Scholar 

  • Breslow N, Chan CW, Dhom G, Drury RA, Franks LM, Gellei B, Lee YS, Lundberg S, Sparke B, Sternby NH, Tulinius H (1977) Latent carcinoma of prostate at autopsy in seven areas. The international agency for research on cancer, Lyons, France. Int J Cancer 20(5):680–688

    Article  PubMed  CAS  Google Scholar 

  • Brigelius-Flohe R, Traber MG (1999) Vitamin E: function and metabolism. FASEB J 13:1145–1155

    PubMed  CAS  Google Scholar 

  • Campbell SE, Stone WL, Lee S, Whaley S, Yang H, Qui M, Goforth P, Sherman D, McHaffie D, Krishnan K (2006) Comparative effects of RRR-∝ and RRR-γ-tocopherol on proliferation and apoptosis in human colon cancer cell lines. BMC Cancer 6:13

    Article  PubMed  Google Scholar 

  • Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572

    Article  PubMed  CAS  Google Scholar 

  • Chan JM, Stampfer MJ, Giovannucci EL (1998) What causes prostate cancer? A brief summary of the epidemiology. Semin Cancer Biol 8(4):263–273

    Article  PubMed  CAS  Google Scholar 

  • Chan R, Lok K, Woo J (2009) Prostate cancer and vegetable consumption. Mol Nutr Food Res 53(2):201–216

    Article  PubMed  CAS  Google Scholar 

  • Chen LH, Boissonneault GA, Glauert HP (1988) Vitamin C, vitamin F and cancer. Anticancer Res 8:739–748

    PubMed  CAS  Google Scholar 

  • Clarke DD, Mycek MJ, Neidle A, Waelsch H (1957) The incorporation of amines into proteins. Arch Biochem Biophys 79:338–354

    Article  Google Scholar 

  • Davies G, Ablin RJ, Mason MD, Jiang WG (2007) Expression of the prostate transglutaminase (TGase-4) in prostate cancer cells and its impact on the invasiveness of prostate cancer. J Exp Ther Oncol 6(3):257–264

    PubMed  CAS  Google Scholar 

  • Dubbink HJ, Verkaik NS, Faber PW, Trapman J, Schroder FH, Romijn JC (1996) Tissue-specific and androgen-regulated expression of human prostate-specific transglutaminase. Biochem J 315:901–908

    PubMed  CAS  Google Scholar 

  • Dubbink HJ, Hoedemaeker RF, van der Kwast TH, Schroder F, Romijn JC (1999) Human prostate-specific transglutaminase: a new prostatic marker with a unique distribution pattern. Lab Invest 79:141–150

    PubMed  CAS  Google Scholar 

  • Eichholzer M, Stahelin HB, Gey KF, Ludin E, Bernasconi F (1996) Prediction of male cancer mortality by plasma levels of interacting vitamins: 17-year follow-up of the prospective Basel study. Int J Cancer 66:145–150

    Article  PubMed  CAS  Google Scholar 

  • Fesus L, Piacentini M (2002) Transglutaminase 2: an enigmatic enzyme with diverse functions. Trends Biochem Sci 27(10):534–539

    Article  PubMed  CAS  Google Scholar 

  • Fitzpatrick JM (2008) Management of localized prostate cancer in senior adults: the crucial role of comorbidity. BJU Int 101(Suppl. 2):16–22

    Article  PubMed  Google Scholar 

  • Folk JE, Finlayson JS (1977) The ε-(γ-glutamyl)lysine crosslink and the catalytic role of transglutaminase. Adv Prot Chem 31:1–133

    Article  CAS  Google Scholar 

  • Gábor M (1986) Anti-inflammatory and anti-allergic properties of flavonoids. Prog Clin Biol Res 213:471–480

    PubMed  Google Scholar 

  • Gao K, Henning SM, Niu Y, Youssefian AA, Seeram NP, Xu A, Heber D (2006) The citrus flavonoid naringenin stimulates DNA repair in prostate cancer cells. J Nutr Biochem 17(2):89–95

    Article  PubMed  CAS  Google Scholar 

  • Geng H, Rademacher BL, Pittsenbarger J, Huang CY, Harvey CT, Lafortune MC, Myrthue A, Garzotto M, Nelson PS, Beer TM, Qian DZ (2010) ID1 enhances docetaxel cytotoxicity in prostate cancer cells through inhibition of p21. Cancer Res 70:3239–3248

    Article  PubMed  CAS  Google Scholar 

  • Gopalakrishnan A, Xu CJ, Nair SS, Chen C, Hebbar V, Kong AN (2006) Modulation of activator protein-1 (AP-1) and MAPK pathway by flavonoids in human prostate cancer PC3 cells. Arch Pharm Res 29(8):633–644

    Article  PubMed  CAS  Google Scholar 

  • Gunawardena K, Murray DK, Meikle AW (2000) Vitamin E and other antioxidants inhibit human prostate cancer cells through apoptosis. Prostate 44:287–295

    Article  PubMed  CAS  Google Scholar 

  • Hamalainen E, Adlercreutz H, Puska P, Pietinen P (1983) Decrease of serum total and free testosterone during a low-fat high-fibre diet. J Steroid Biochem 18:369–370

    Article  PubMed  CAS  Google Scholar 

  • Iemelynova AA, Grygorenko VM, Cheremuha SV, Romanenko AM (2009) Correlation between histological type and immunohistochemical profile of prostate cancer and gleason scale gradation. Exp Oncol 31:246–249

    PubMed  CAS  Google Scholar 

  • Israel K, Sanders BG, Kline K (1995) RRR-alpha-tocopheryl succinate inhibits the proliferation of human prostatic tumor cells with defective cell cycle/differentiation pathways. Nutr Cancer 24:161–169

    Article  PubMed  CAS  Google Scholar 

  • Jimenez JJ, Yunis AA (1987) Tumor cell rejection through terminal cell differentiation. Science 238:1278–1280

    Article  PubMed  CAS  Google Scholar 

  • Knekt P (1988) Serum alpha-tocopherol, the risk of cancer, vol 83. Publications of the Social Insurance Institution, Helsinki, pp 1–148

    Google Scholar 

  • Knekt P, Aromaa A, Maatela J, Aaran RK, Nikkari T, Hakama M, Hakulinen T, Peto R, Teppo L (1991) Vitamin E and cancer prevention. Am J Clin Nutr 53(1 Suppl):283S–286S

    PubMed  CAS  Google Scholar 

  • Lentini A, Forni C, Provenzano B, Beninati S (2007) Enhancement of transglutaminase activity and polyamine depletion in B16–F10 melanoma cells by flavonoids naringenin and hesperitin correlate to reduction of the in vivo metastatic potential. Amino Acids 32:95–100

    Article  PubMed  CAS  Google Scholar 

  • Lentini A, Provenzano B, Tabolacci C, Beninati S (2009) Protein–polyamine conjugates by transglutaminase 2 as potential markers for antineoplastic screening of natural compounds. Amino Acids 36(4):701–708

    Article  PubMed  CAS  Google Scholar 

  • Lentini A, Tabolacci C, Provenzano B, Rossi S, Beninati S (2010) Phytochemicals and protein-polyamine conjugates by transglutaminase as chemopreventive and chemotherapeutic tools in cancer. Plant Physiol Biochem 48(7):627–633

    Article  PubMed  CAS  Google Scholar 

  • Leszczyniecka M, Roberts T, Dent P, Grant S, Fisher PB (2001) Differentiation therapy of human cancer: basic science and clinical applications. Pharm Therap 90:105–156

    Article  CAS  Google Scholar 

  • Luzzi KJ, MacDonald IC, Schmidt EE, Kerkvliet N, Morris VL, Chambers AF, Groom AC (1998) Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol 153:865–873

    Article  PubMed  CAS  Google Scholar 

  • Nakamura A, Shirai T, Takahashi S, Ogawa K, Hirose M, Ito N (1991) Lack of modification by naturally occurring antioxidants of 3, 2’-dimethyl-4-aminobiphenyl-initiated rat prostate carcinogenesis. Cancer Lett 58:241–246

    Article  PubMed  CAS  Google Scholar 

  • Ni J, Chen M, Zhang Y, Li R, Huang J, Yeh S (2003) Vitamin E succinate inhibits human prostate cancer cell growth via modulating cell cycle regulatory machinery. Biochem Biophys Res Commun 300:357–363

    Article  PubMed  CAS  Google Scholar 

  • Packer L (1991) Protective role of vitamin E in biological systems. Am J Clin Nutr 53:1050S–1055S

    PubMed  CAS  Google Scholar 

  • Sies H, Murphy ME (1991) Role of tocopherols in the protection of biological systems against oxidative damage. J Photochem Photobiol B 8:211–218

    Article  PubMed  CAS  Google Scholar 

  • Spina AM, Esposito C, Pagano M, Chiosi E, Mariniello L, Cozzolino A, Porta R, Illiano G (1999) GTPase and transglutaminase are associated in the secretion of the rat anterior prostate. Biochem Biophys Res Commun 260:351–356

    Article  PubMed  CAS  Google Scholar 

  • Stangelberger A, Waldert M, Djavan B (2008) Prostate cancer in elderly men. Rev Urol 10:111–119

    PubMed  Google Scholar 

  • Thiele CJ, Gore S, Collins S, Waxman S, Miller W (2000) Differentiate or die: the view from Montreal. Cell Death Differ 7:1014–1017

    Article  PubMed  CAS  Google Scholar 

  • Venkateswaran V, Fleshner NE, Klotz LH (2002) Modulation of cell proliferation and cell cycle regulators by vitamin E in human prostate carcinoma cell lines. J Urol 168:1578–1582

    Article  PubMed  CAS  Google Scholar 

  • Venkateswaran V, Fleshner NE, Sugar LM, Klotz LH (2004) Antioxidants block prostate cancer in lady transgenic mice. Cancer Res 64:5891–5896

    Article  PubMed  CAS  Google Scholar 

  • Virtamo J, Pietinen P, Huttunen JK, Korhonen P, Malila N, Virtanen MJ, Albanes D, Taylor PR, Albert P (2003) Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. JAMA 290:476–485

    Article  PubMed  CAS  Google Scholar 

  • Williams-Ashman HG (1984) Transglutaminases and the clotting of mammalian seminal fluids. Mol Cell Biochem 58:51–61

    Article  PubMed  CAS  Google Scholar 

  • Yin M, Bastacky S, Chandran UE, Becich MJ, Dhir R (2008) Prevalence of incidental prostate cancer in the general population: a study of healthy organ donors. J Urol 179:892–895

    Article  PubMed  Google Scholar 

  • Zu K, Ip C (2003) Synergy between selenium and vitamin E in apoptosis induction is associated with activation of distinctive initiator caspases in human prostate cancer cells. Cancer Res 63:6988–6995

    PubMed  CAS  Google Scholar 

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Acknowledgments

We thanks Prof. Salvatore Passarella for assistance and helpful discussion.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department SPES, University of Molise, Campobasso, Italy

    Piera Torricelli & Pasquale Ricci

  2. Department of Biology, University of Rome “Tor Vergata”, Rome, Italy

    Bruno Provenzano, Alessandro Lentini & Claudio Tabolacci

Authors
  1. Piera Torricelli
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  2. Pasquale Ricci
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  3. Bruno Provenzano
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  4. Alessandro Lentini
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  5. Claudio Tabolacci
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Correspondence to Piera Torricelli.

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Torricelli, P., Ricci, P., Provenzano, B. et al. Synergic effect of α-tocopherol and naringenin in transglutaminase-induced differentiation of human prostate cancer cells. Amino Acids 41, 1207–1214 (2011). https://doi.org/10.1007/s00726-010-0788-8

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  • DOI: https://doi.org/10.1007/s00726-010-0788-8

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