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Role of Capsaicin in Prostate Cancer

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Role of Capsaicin in Oxidative Stress and Cancer

Part of the book series: Diet and Cancer ((DICA,volume 3))

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Abstract

In the recent years, natural products have emerged as modulators of many cellular responses with potential applications as therapeutic drugs in many disorders. Among them, capsaicin, the pungent principle of chili peppers, has received an increasing attention for its strong chemo-preventive and chemotherapeutic ability in recent few years. In this chapter some of the molecular and cellular events initiated by treatment of prostate cancer cells with capsaicin are addressed and the potential role of capsaicin signaling network as target for prostate cancer treatment is discussed. Capsaicin induces cell cycle arrest and apoptosis in the androgen-insensitive prostate cancer PC-3 and DU-145 cell lines. Among the pathways underlying the mechanisms of action of capsaicin, ROS generation and ceramide accumulation seem to be the most relevant. In prostate PC-3 cells, capsaicin also induces endoplasmic reticulum stress and caspase-3 activation. Moreover, capsaicin exhibits anti-tumor growth activity in prostate tumors induced in mice. The data suggest that capsaicin holds promise as a treatment option for prostate cancer.

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References

  • Andela VB, Gordon AH, Zotalis G et al (2003) Nfkappab: a pivotal transcription factor in prostate cancer metastasis to bone. Clin Orthop Relat Res 415 Suppl:S75–85

    Article  PubMed  Google Scholar 

  • Athanasiou A, Smith PA, Vakilpour S et al (2007) Vanilloid receptor agonists and antagonists are mitochondrial inhibitors: how vanilloids cause non-vanilloid receptor mediated cell death. Biochem Biophys Res Commun 354(1):50–55

    Article  PubMed  CAS  Google Scholar 

  • Bartke N, Hannun YA (2009) Bioactive sphingolipids: metabolism and function. J Lipid Res 50(Suppl):S91–96

    Article  PubMed  Google Scholar 

  • Bartoletti R, Gavazzi A, Cai T et al (2009) Prostate growth and prevalence of prostate diseases in early onset spinal cord injuries. Eur Urol 56(1):142–148

    Article  PubMed  Google Scholar 

  • Bidaux G, Roudbaraki M, Merle C et al (2005) Evidence for specific trpm8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement. Endocr Relat Cancer 12(2):367–382

    Article  PubMed  CAS  Google Scholar 

  • Bieberich E (2004) Integration of glycosphingolipid metabolism and cell-fate decisions in cancer and stem cells: review and hypothesis. Glycoconj J 21(6):315–327

    Article  PubMed  CAS  Google Scholar 

  • Bohlen CJ, Priel A, Zhou S, King D, Siemens J, Julius D (2010) A bivalent tarantula toxin activates the capsaicin receptor, trpv1, by targeting the outer pore domain. Cell 141(5):834–845

    Article  PubMed  CAS  Google Scholar 

  • Brooks DD, Wolf A, Smith RA, Dash C, Guessous I (2010) Prostate cancer screening 2010: updated recommendations from the american cancer society. J Natl Med Assoc 102(5):423–429

    PubMed  Google Scholar 

  • Caterina MJ, Julius D (2001) The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 24:487–517

    Article  PubMed  CAS  Google Scholar 

  • Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389(6653):816–824

    Article  PubMed  CAS  Google Scholar 

  • Chow J, Norng M, Zhang J, Chai J (2007) Trpv6 mediates capsaicin-induced apoptosis in gastric cancer cells – mechanisms behind a possible new “Hot” cancer treatment. Biochim Biophys Acta 1773(4):565–576

    Article  PubMed  CAS  Google Scholar 

  • Chuang YC, Yoshimura N, Wu M et al (2007) Intraprostatic capsaicin injection as a novel model for nonbacterial prostatitis and effects of botulinum toxin a. Eur Urol 51(4):1119–1127

    Article  PubMed  CAS  Google Scholar 

  • Chuang YC, Yoshimura N, Huang CC, Wu M, Chiang PH, Chancellor MB (2008) Intraprostatic botulinum toxin a injection inhibits cyclooxygenase-2 expression and suppresses prostatic pain on capsaicin induced prostatitis model in rat. J Urol 180(2):742–748

    Article  PubMed  CAS  Google Scholar 

  • Crane FL, Low H (2008) Reactive oxygen species generation at the plasma membrane for antibody control. Autoimmun Rev 7(7):518–522

    Article  PubMed  CAS  Google Scholar 

  • Cui J, Bian JS, Kagan A, Mcdonald TV (2002) Cat1 contributes to the stores-operated calcium current in jurkat t-lymphocytes. J Biol Chem 277(49):47175–47183

    Article  PubMed  CAS  Google Scholar 

  • Czifra G, Varga A, Nyeste K et al (2009) Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma. J Cancer Res Clin Oncol 135(4):507–514

    Article  PubMed  CAS  Google Scholar 

  • De Luca T, Morre DM, Zhao H, Morre DJ (2005) Nad+/nadh and/or coq/coqh2 ratios from plasma membrane electron transport may determine ceramide and sphingosine-1-phosphate levels accompanying g1 arrest and apoptosis. Biofactors 25(1–4):43–60

    Article  PubMed  Google Scholar 

  • Dinis P, Charrua A, Avelino A et al (2005) The distribution of sensory fibers immunoreactive for the trpv1 (capsaicin) receptor in the human prostate. Eur Urol 48(1):162–167

    Article  PubMed  Google Scholar 

  • Fernandez-Ballester G, Ferrer-Montiel A (2008) Molecular modeling of the full-length human trpv1 channel in closed and desensitized states. J Membr Biol 223(3):161–172

    Article  PubMed  CAS  Google Scholar 

  • Ferrer-Montiel A, Garcia-Martinez C, Morenilla-Palao C et al (2004) Molecular architecture of the vanilloid receptor. Insights for drug design. Eur J Biochem 271(10):1820–1826

    Article  PubMed  CAS  Google Scholar 

  • Fixemer T, Wissenbach U, Flockerzi V, Bonkhoff H (2003) Expression of the ca2+-selective cation channel trpv6 in human prostate cancer: a novel prognostic marker for tumor progression. Oncogene 22(49):7858–7861

    Article  PubMed  CAS  Google Scholar 

  • Fizazi K, Sternberg CN, Fitzpatrick JM, Watson RW, Tabesh M (2010) Role of targeted therapy in the treatment of advanced prostate cancer. BJU Int 105(6):748–767

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Cao I, Duran A, Collado M et al (2005) Tumour-suppression activity of the proapoptotic regulator par4. EMBO Rep 6(6):577–583

    Article  PubMed  CAS  Google Scholar 

  • Gratzke C, Weinhold P, Reich O et al (2010) Transient receptor potential a1 and cannabinoid receptor activity in human normal and hyperplastic prostate: relation to nerves and interstitial cells. Eur Urol 57(5):902–910

    Article  PubMed  Google Scholar 

  • Hail N Jr (2003) Mechanisms of vanilloid-induced apoptosis. Apoptosis 8(3):251–262

    Article  PubMed  CAS  Google Scholar 

  • Henshall SM, Afar DE, Hiller J et al (2003) Survival analysis of genome-wide gene expression profiles of prostate cancers identifies new prognostic targets of disease relapse. Cancer Res 63(14):4196–4203

    PubMed  CAS  Google Scholar 

  • Horoszewicz JS, Leong SS, Kawinski E et al (1983) Lncap model of human prostatic carcinoma. Cancer Res 43(4):1809–1818

    PubMed  CAS  Google Scholar 

  • Iype PT, Iype LE, Verma M, Kaighn ME (1998) Establishment and characterization of immortalized human cell lines from prostatic carcinoma and benign prostatic hyperplasia. Int J Oncol 12(2):257–263

    PubMed  CAS  Google Scholar 

  • Jankovic B, Loblaw DA, Nam R (2010) Capsaicin may slow psa doubling time: case report and literature review. Can Urol Assoc J 4(1):E9–E11

    PubMed  Google Scholar 

  • Jiang Z, Gorenstein NM, Morre DM, Morre DJ (2008) Molecular cloning and characterization of a candidate human growth-related and time-keeping constitutive cell surface hydroquinone (nadh) oxidase. Biochemistry 47(52):14028–14038

    Article  PubMed  CAS  Google Scholar 

  • Jordt SE, Tominaga M, Julius D (2000) Acid potentiation of the capsaicin receptor determined by a key extracellular site. Proc Natl Acad Sci USA 97(14):8134–8139

    Article  PubMed  CAS  Google Scholar 

  • Jung J, Hwang SW, Kwak J et al (1999) Capsaicin binds to the intracellular domain of the capsaicin-activated ion channel. J Neurosci 19(2):529–538

    PubMed  CAS  Google Scholar 

  • Kuramori C, Azuma M, Kume K et al (2009) Capsaicin binds to prohibitin 2 and displaces it from the mitochondria to the nucleus. Biochem Biophys Res Commun 379(2):519–525

    Article  PubMed  CAS  Google Scholar 

  • Lallet-Daher H, Roudbaraki M, Bavencoffe A et al (2009) Intermediate-conductance ca2+-activated k+ channels (ikca1) regulate human prostate cancer cell proliferation through a close control of calcium entry. Oncogene 28(15):1792–1806

    Article  PubMed  CAS  Google Scholar 

  • Lehen’kyi V, Flourakis M, Skryma R, Prevarskaya N (2007) Trpv6 channel controls prostate cancer cell proliferation via ca(2+)/nfat-dependent pathways. Oncogene 26(52):7380–7385

    Article  PubMed  Google Scholar 

  • Lishko PV, Procko E, Jin X, Phelps CB, Gaudet R (2007) The ankyrin repeats of trpv1 bind multiple ligands and modulate channel sensitivity. Neuron 54(6):905–918

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Cheng JC, Turner LS et al (2009) Acid ceramidase upregulation in prostate cancer: role in tumor development and implications for therapy. Expert Opin Ther Targets 13(12):1449–1458

    Article  PubMed  CAS  Google Scholar 

  • Macho A, Calzado MA, Munoz-Blanco J et al (1999) Selective induction of apoptosis by capsaicin in transformed cells: the role of reactive oxygen species and calcium. Cell Death Differ 6(2):155–165

    Article  PubMed  CAS  Google Scholar 

  • Macho A, Sancho R, Minassi A, Appendino G, Lawen A, Munoz E (2003) Involvement of reactive oxygen species in capsaicinoid-induced apoptosis in transformed cells. Free Radic Res 37(6):611–619

    Article  PubMed  CAS  Google Scholar 

  • Malagarie-Cazenave S, Olea-Herrero N, Vara D, Diaz-Laviada I (2009) Capsaicin, a component of red peppers, induces expression of androgen receptor via pi3k and mapk pathways in prostate lncap cells. FEBS Lett 583(1):141–147

    Article  PubMed  CAS  Google Scholar 

  • Messeguer A, Planells-Cases R, Ferrer-Montiel A (2006) Physiology and pharmacology of the vanilloid receptor. Curr Neuropharmacol 4(1):1–15

    Article  PubMed  CAS  Google Scholar 

  • Monet M, Lehen’kyi V, Gackiere F et al (2010) Role of cationic channel trpv2 in promoting prostate cancer migration and progression to androgen resistance. Cancer Res 70(3):1225–1235

    Article  PubMed  CAS  Google Scholar 

  • Montell C, Birnbaumer L, Flockerzi V (2002) The trp channels, a remarkably functional family. Cell 108(5):595–598

    Article  PubMed  CAS  Google Scholar 

  • Mori A, Lehmann S, O’kelly J et al (2006) Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells. Cancer Res 66(6):3222–3229

    Article  PubMed  CAS  Google Scholar 

  • Morre DJ, Morre DM (2006) Aging-related cell surface ecto-nox protein, arnox, a preventive target to reduce atherogenic risk in the elderly. Rejuvenation Res 9(2):231–236

    Article  PubMed  CAS  Google Scholar 

  • Morre DJ, Chueh PJ, Morre DM (1995) Capsaicin inhibits preferentially the nadh oxidase and growth of transformed cells in culture. Proc Natl Acad Sci USA 92(6):1831–1835

    Article  PubMed  CAS  Google Scholar 

  • Morre DJ, Sun E, Geilen C et al (1996) Capsaicin inhibits plasma membrane nadh oxidase and growth of human and mouse melanoma lines. Eur J Cancer 32A(11):1995–2003

    Article  PubMed  CAS  Google Scholar 

  • Morre DJ, Caldwell S, Mayorga A, Wu LY, Morre DM (1997) Nadh oxidase activity from sera altered by capsaicin is widely distributed among cancer patients. Arch Biochem Biophys 342(2):224–230

    Article  PubMed  CAS  Google Scholar 

  • Morre DJ, Morre DM, Shelton TB (2010) Aging-related nicotinamide adenine dinucleotide oxidase response to dietary supplementation: the french paradox revisited. Rejuvenation Res 13(2–3):159–161

    Article  PubMed  CAS  Google Scholar 

  • Ozbayraktar FB, Ulgen KO (2009) Molecular facets of sphingolipids: mediators of diseases. Biotechnol J 4(7):1028–1041

    Article  PubMed  CAS  Google Scholar 

  • Palayoor ST, Youmell MY, Calderwood SK, Coleman CN, Price BD (1999) Constitutive activation of ikappab kinase alpha and nf-kappab in prostate cancer cells is inhibited by ibuprofen. Oncogene 18(51):7389–7394

    Article  PubMed  CAS  Google Scholar 

  • Peng JB, Zhuang L, Berger UV et al (2001) Cat1 Expression correlates with tumor grade in prostate cancer. Biochem Biophys Res Commun 282(3):729–734

    Article  PubMed  CAS  Google Scholar 

  • Phelps CB, Procko E, Lishko PV, Wang RR, Gaudet R (2007) Insights into the roles of conserved and divergent residues in the ankyrin repeats of trpv ion channels. Channels (Austin) 1(3):148–151

    Google Scholar 

  • Prevarskaya N, Zhang L, Barritt G (2007) Trp channels in cancer. Biochim Biophys Acta 1772(8):937–946

    Article  PubMed  CAS  Google Scholar 

  • Rho YW, Bae YS (2010) Capsaicin, a component of red peppers, stimulates protein kinase ckii activity. BMB Rep 43(5):325–329

    Article  PubMed  CAS  Google Scholar 

  • Sanchez MG, Sanchez AM, Collado B et al (2005) Expression of the transient receptor potential vanilloid 1 (trpv1) in lncap and pc-3 prostate cancer cells and in human prostate tissue. Eur J Pharmacol 515(1–3):20–27

    Article  PubMed  CAS  Google Scholar 

  • Sanchez AM, Sanchez MG, Malagarie-Cazenave S, Olea N, Diaz-Laviada I (2006) Induction of apoptosis in prostate tumor pc-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin. Apoptosis 11(1):89–99

    Article  PubMed  CAS  Google Scholar 

  • Sanchez AM, Malagarie-Cazenave S, Olea N, Vara D, Chiloeches A, Diaz-Laviada I (2007) Apoptosis induced by capsaicin in prostate pc-3 cells involves ceramide accumulation, neutral sphingomyelinase, and jnk activation. Apoptosis 12(11):2013–2024

    Article  PubMed  CAS  Google Scholar 

  • Sanchez AM, Martinez-Botas J, Malagarie-Cazenave S et al (2008) Induction of the endoplasmic reticulum stress protein gadd153/chop by capsaicin in prostate pc-3 cells: a microarray study. Biochem Biophys Res Commun 372(4):785–791

    Article  PubMed  CAS  Google Scholar 

  • Sells SF, Wood DP Jr, Joshi-Barve SS et al (1994) Commonality of the gene programs induced by effectors of apoptosis in androgen-dependent and -independent prostate cells. Cell Growth Differ 5(4):457–466

    PubMed  CAS  Google Scholar 

  • Sells SF, Han S, Muthukkumar S et al (1997) Expression and function of the leucine zipper protein par-4 in apoptosis. Mol Cell Biol 17(7):3823–3832

    PubMed  CAS  Google Scholar 

  • Sikka SC, Huang L et al (2010) Novel role for the transient receptor potential channel trpm2 in prostate cancer cell proliferation. Prostate Cancer Prostatic Dis 13(2):195–201

    Article  PubMed  Google Scholar 

  • Stavridi F, Karapanagiotou EM, Syrigos KN (2010) Targeted therapeutic approaches for hormone-refractory prostate cancer. Cancer Treat Rev 36(2):122–130

    Article  PubMed  CAS  Google Scholar 

  • Stone KR, Mickey DD, Wunderli H, Mickey GH, Paulson DF (1978) Isolation of a human prostate carcinoma cell line (du 145). Int J Cancer 21(3):274–281

    Article  PubMed  CAS  Google Scholar 

  • Szallasi A (2001) Vanilloid receptor ligands: hopes and realities for the future. Drugs Aging 18(8):561–573

    Article  PubMed  CAS  Google Scholar 

  • Tsavaler L, Shapero MH, Morkowski S, Laus R (2001) Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res 61(9):3760–3769

    PubMed  CAS  Google Scholar 

  • Ursu D, Knopp K, Beattie RE, Liu B, Sher E (2010) Pungency of trpv1 agonists is directly correlated with kinetics of receptor activation and lipophilicity. Eur J Pharmacol 641(2–3):114–122

    Article  PubMed  CAS  Google Scholar 

  • Van Der Aa F, Roskams T, Blyweert W, De Ridder D (2003) Interstitial cells in the human prostate: a new therapeutic target? Prostate 56(4):250–255

    Article  PubMed  Google Scholar 

  • Vriens J, Appendino G, Nilius B (2009) Pharmacology of vanilloid transient receptor potential cation channels. Mol Pharmacol 75(6):1262–1279

    Article  PubMed  CAS  Google Scholar 

  • Walpole CS, Wrigglesworth R, Bevan S et al (1993) Analogues of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain “C-region”. J Med Chem 36(16):2381–2389

    Article  PubMed  CAS  Google Scholar 

  • Walpole CS, Bevan S, Bloomfield G et al (1996) Similarities and differences in the structure-activity relationships of capsaicin and resiniferatoxin analogues. J Med Chem 39(15):2939–2952

    Article  PubMed  CAS  Google Scholar 

  • Wang HP, Pu XY, Wang XH (2007) Distribution profiles of transient receptor potential melastatin-related and vanilloid-related channels in prostatic tissue in rat. Asian J Androl 9(5):634–640

    Article  PubMed  Google Scholar 

  • Wang G, Yang ZQ, Zhang K (2010) Endoplasmic reticulum stress response in cancer: molecular mechanism and therapeutic potential. Am J Transl Res 2(1):65–74

    PubMed  Google Scholar 

  • Webber MM, Bello D, Quader S (1997) Immortalized and tumorigenic adult human prostatic epithelial cell lines: characteristics and applications part 2. Tumorigenic cell lines. Prostate 30(1):58–64

    Article  PubMed  CAS  Google Scholar 

  • Wissenbach U, Niemeyer BA (2007) Trpv6. Handb Exp Pharmacol 179:221–234

    Article  PubMed  CAS  Google Scholar 

  • Wissenbach U, Niemeyer BA, Fixemer T et al (2001) Expression of cat-like, a novel calcium-selective channel, correlates with the malignancy of prostate cancer. J Biol Chem 276(22):19461–19468

    Article  PubMed  CAS  Google Scholar 

  • Wissenbach U, Niemeyer B, Himmerkus N, Fixemer T, Bonkhoff H, Flockerzi V (2004) Trpv6 And prostate cancer: cancer growth beyond the prostate correlates with increased trpv6 ca2+ channel expression. Biochem Biophys Res Commun 322(4):1359–1363

    Article  PubMed  CAS  Google Scholar 

  • Yang ZH, Wang XH, Wang HP, Hu LQ (2009) Effects of trpm8 on the proliferation and motility of prostate cancer pc-3 cells. Asian J Androl 11(2):157–165

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Barritt GJ (2004) Evidence that trpm8 is an androgen-dependent ca2+ channel required for the survival of prostate cancer cells. Cancer Res 64(22):8365–8373

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Barritt GJ (2006) Trpm8 in prostate cancer cells: a potential diagnostic and prognostic marker with a secretory function? Endocr Relat Cancer 13(1):27–38

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by Ministerio de Ciencia e Innovación (grant SAF2008-03220), Comunidad de Madrid (grants CAM/UAH CCG08-UAH/BIO-3914 and CAM S-SAL-0261-2006) and Comunidad Castilla-LaMancha (Grant PII1/09-0165-0822).

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  1. Department of Biochemistry and Molecular Biology, School of Medicine, University of Alcalá, Alcalá de Henares, 28871, Madrid, Spain

    Inés Díaz-Laviada

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  1. Inés Díaz-Laviada
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Correspondence to Inés Díaz-Laviada .

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  1. , Biomedical Sciences, Texas Tech Univ. Health Sciences Center, Coulter Drive 1406, Amarillo, 79106, Texas, USA

    Sanjay K. Srivastava

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Díaz-Laviada, I. (2013). Role of Capsaicin in Prostate Cancer. In: Srivastava, S. (eds) Role of Capsaicin in Oxidative Stress and Cancer. Diet and Cancer, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6317-3_3

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  • DOI: https://doi.org/10.1007/978-94-007-6317-3_3

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